The Drugs (Licensing, Registring and Advertising) Rules, 1976

DRUGS (LICENSING, REGISTERING AND ADVERTISING)

RULES, 1976

S.R.O. 145 (I)/76 dated 12th February 1976:- In exercise of the powers conferred by Section 41 of the Drugs Ordinance, 1976 (IV of 1976), the Federal Government is pleased to make the following rules, namely :--

CHAPTER I - PRELIMINARY 1. Short title and commencement: .(1) These rules may be called the Drugs (Licensing, Registering and Advertising) Rules, 1976. (2) They shall come into force at once. 2. Definitions.-- In these rules, unless there is anything repugnant in the subject or context:-- (a) "active pharmaceutical ingredient" means a substance or compound that is intended to be used in the manufacture of a pharmaceutical product as a pharmacologically active compound (ingredient); (b) "airlock" means an enclosed space with two or more doors, which is interposed between two or more rooms of differing classes of cleanliness for the purpose of controlling the airflow between those rooms when they need to be entered and an airlock is designed for and used by either people or goods; (c) "authorized person" means a person responsible for the release of batches of product for sale; (d) "basic manufacture" means manufacture of a drug from basic raw material to a product which is ready for use as a starting material for the formulation of a finished drug or for repacking and such manufacture may involve chemical, bio-chemical, photochemical, microbial or such other processes or a combination of any of such processes; (e) "batch (or lot)" means a defined quantity of starting material, packaging material, or finish product processed in a single process or series of processes so that it could be expected to be homogeneous in the case of continuous manufacture the batch must correspond to a defined fraction of the production, characterized by its intended homogeneity, and to complete certain stages of manufacture it may sometimes be necessary to divide a batch into a number of sub-batches, which are later brought together to from a final homogeneous batch; (f) "batch number (or lot number)" means a distinctive combination of numbers and or letters which specifically identifies a batch on the labels, the batch records, the certificates of analysis, and that permit the production history of the batch to be traced and revived. (g) "batch numbering system" means a standard operating procedure describing the details of the batch numbering; (h) "batch records" means all documents associated with the manufacture of a batch of bulk product or finished product showing a history of each batch of product and of all circumstances pertinent to the quality of the final product; (i) "biological agents" means micro-organisms, including genetically engineered micro-organisms, cell cultures and endoparasites, whether pathogenic or not; (j) "bulk product" means any product that has completed all processing stages up to, but not including, final packaging; (k) "calibration" means the set of operations that establish, under specified conditions, the relationship between values indicated by a instrument or measuring system for especially weighing, recording and controlling, or the values represented by a material measure and the corresponding known values of a reference standard and the limits for acceptance of the results of measuring; (l) "clean area" means an area with defined environmental control of particulate and microbial contamination, constructed and used in such a way as to reduce and or eliminate introduction, generation and retention of contaminants within the area; (m) "compounding" means scientific combination of two or more ingredients with a view to make a finished drug; (n) "consignment or delivery" means the quantity of starting material or of a drug product, made by one manufacturer and supplied one time in response to a particular request or order, a consignment may comprise one or more packages or containers and may include material belonging to more than one batch; (o) "critical process" means a process that may cause variation in the quality of the pharmaceutical product; (p) "cross-contamination" means contamination of a staring material intermediate product, or finished product with another starting material or drug during production; (q) "finished product" means a product that has undergone all stages of production, including packaging in its final container and labeling; (r) "Form" means a form set forth in Schedule A; (s) "formulation" means all operations involved in converting a drug into a final pharmaceutical dosage form ready for use as a finished drug including compounding, processing, formulating, filling, packing, finishing, labelling and other like processes; (t) "good manufacturing practices for pharmaceutical products" means part of quality assurance which:-- (i) ensure that products are consistently produced and controlled to the quality standards appropriate to their intended use are as required by the marketing authorization or product specification; and (ii) diminish the risks, inherent in any pharmaceutical production, including contamination, cross contamination and mix ups (confusion) that cannot be detected completely through the testing of final products; (u) "half-finished product" means any material or mixture of materials that has to undergo further manufacture; (v) "in-process control" means checks performed during production in order to monitor and if necessary to adjust the process to ensure that the product conforms to its specifications and control of the environment or equipment may also be regarded as a part of in-process control; (w) "intermediate product" means partly processed material that must undergo further manufacturing steps before it becomes a bulk product; (x) "large-volume parenterals" means sterile solutions intended for parenteral application with a volume of more than 100ml in one container of the finished dosage form; (y) "manufacture" means all operations of production, quality control, release, storage and the related controls; (z) "manufacturer" means a company that carries out at least one step of manufacture; (aa) "marketing authorization" means a document, issued by the Drug Registration Board set up under the Drugs Act, 1976, as a certificate of drug registration; (ab) "master formula" means a document or set of documents specifying the starting materials with their quantities and the packaging materials, together with a description of the procedure and precautions required to produce a specified quantity of a finished product as well as the processing instructions, including the in-process controls; (ac) "master record" means a document or set of documents that serve as a basis for the batch documentation (blank batch record); (ad) "new drug" means a drug that has not been commonly sold or distributed to the public in Pakistan and is introduced for the first time; (ae) "Ordinance" means the Drugs Ordinance, 1976 (IV of 1976); (af) "packaging" means all operations, including filling and labelling which a bulk drug has to undergo in order to become a finished product; Note: Sterile filling would not normally be regarded as part of packaging, the bulk product being the filled, but not the finally packaged, primary container. (ag) "packaging material" means any material, including printed material, employed in the packaging of a pharmaceutical product, excluding any outer packaging used for transportation or shipment and packaging materials are referred to as primary or secondary according to whether or not they are intended to be in direct contact with the product; (ah) "pharmaceutical product" means any drug intended for human use or veterinary use presented in its finished dosage form or as a starting material for use in such a dosage form; (ai) "processing instructions or procedures" means a defined in clause (ab) of this section; (aj) "production" means all operations involved in the preparation of a pharmaceutical product, from receipt of materials, through processing and packaging, to its completion as the finished product; (ak) "purity" means the degree to which other chemical or biological entities are present in any substance; (al) "quality assurance" means the totality of the arrangements made with the object of ensuring that pharmaceutical products are of the quality required for their intended use and so incorporates good manufacturing practices, Quality Control and other factors including product design and development and good laboratory practices; (am) "quality control" means the part of good manufacturing practices concerned with sampling, specifications, and testing as well as the organization, documentation, and release procedures which ensure that the necessary and relevant tests are actually carried out and that materials are not released for use, nor finished products released for sale or supply until their quality has been judged to be satisfactory and it is involved in all decisions concerning the quality of the product; (an) "quarantine" means status of starting or packaging materials intermediate, or bulk or finished products isolated physically or by other effective means while a decision is awaited on their release, rejection, or reprocessing; (ao) "reconciliation" means a comparison, making due allowance for normal variation between the amount of product or materials theoretically produced or used and the amount actually produced or used; (ap) "recovery or blending" means the introduction of all or part of previous batches, or of redistilled solvents and similar products, of the required quality into another batch at a defined stage of manufacture; (aq) "repacking" means all operations involved in the transfer of a drug from a larger container or packing into smaller containers or packings including filling, packing and labeling with a view to make it ready for retail sale or wholesale, but does not includes any compounding, or processing with a view to formulate it in any dosage form; (ar) "retail sale" means a sale other than wholesale; (as) "reprocessing" means the reworking of all or part of a batch of product of an unacceptable quality from a refined stage of production so that its quality may be rendered acceptable by one or more additional operations; (at) "returned product" means finished product sent back to the manufacturer or distributor; (au) "Schedule" means Schedule to these rules; (av) "semi-basic manufacture" means manufacture from an intermediate substance of a drug to be used as a starting material for the formulation of a finished drug or to be used for repacking; (aw) "specification" means the requirements with which the products or materials used or obtained during manufacture must conform as specified in the Drugs (Specification) Rules, 1978; (ax) "standard operating procedure" means an authorized written procedure indicating instructions for performing operations not necessarily specific to a given product or material but of a more general nature such as equipment operation, maintenance and cleaning validation, cleaning of premises and environmental control sampling and inspection, and certain standard operating procedures may be used to supplement product specific master and batch production documentation; (ay) "starting material" means any substance used in the production of a pharmaceutical product but excluding packaging materials; (az) "system" means a regulated pattern of interacting activities and techniques which are united to form an organized whole; (ba) "validation" means the documented act of proving that any procedure, process, equipment, material, activity or system works correctly and actually leads to the expected result; and (bb) "wholesale" means sale to a person who purchases for the purpose of selling again and includes sale to a hospital or dispensary, or to medical, educational or research institute.

CHAPTER II MANUFACTURE OF DRUGS FOR SALE 3. Types of licences to manufacture drugs: Licences to manufacture drugs shall be of the following types, namely :-- (i) licence to manufacture by way of basic manufacture. (ii) licence to manufacture by way of semi-basic manufacture; (iii) licence to manufacture by way of formulation; (iv) licence to manufacture by way of repacking; and (v) licence to manufacture for experimental purposes. 4. Manufacture on more than one set of premises: If drugs are manufactured on more than one set of premises, a separate application shall be made and a separate licence shall be issued in respect of each such set of premises. 5. Application for licence to manufacture drugs and fee therefor: (1) An application for the grant or renewal of a licence referred to in clauses (i) to (iv) of rule 3 shall be made in Form 1 or l-A to the Central Licensing Board addressed to its Secretary. (2) An application under sub-rule (1) shall be accompanied by the proper fee as specified in Schedule F. Proviso: Added vide S.R.O. 536(1)/93 dated 23rd June 1993. Omitted vide S.R.O. 277 (1)/96 dated 2 lst April 1996. (3) If the application for renewal of the licence is made after the expiry of the period of the validity of the licence, it shall be treated as a fresh application for the grant of a licence. (4) A fee of rupees one hundred shall be paid for a duplicate copy of the licence if the original is defaced, damaged or lost. Such copy of the licence shall bear the words "DUPLICATE COPY". (5) Any fee deposited under sub-rule (2) Shall in no case be refunded. 6. Duration of a licence to manufacture drugs: A licence issued under this Chapter shall, unless earlier suspended or cancelled, be inforce for a period of five years from the date of issue and may thereafter be renewed for periods of five years at a time: Provided that an application for renewal shall not be entertained unless it has been made within sixty days after the expiry of the licence and when an application has been made as aforesaid the licence shall subject to the orders passed on the application for renewal continue in force for the next period of two years. Provided further that duration of a licence issued under rule 21 shall be two years unless earlier suspended or cancelled. 7. Certificate of licence to manufacture drugs: A licence to manufacture by way of basic manufacture, semi-basic manufacture, formulation or repacking, as the case may be, shall be issued in Form 2. 8. Central Licensing Board: (1) The Central Licensing Board shall consist of the following members, namely :-- (a) the Director-General Health, Government of Pakistan, who shall be its ex-officio Chairman; (b) the Director, Health Services of, each Provincial Government; (c) two pharmacologists, to be nominated by the Federal Government. (d) one pharmacist, to be nominated by the Federal Government; (e) one medical specialist from the Army Medical Corps. to be nominated by the Federal Government. (f) one pharmaceutical chemist or expert in quality control, to be nominated by the Federal Government; (g) the Drugs Controller, Ministry of Health, Government of Pakistan who shall be its ex-officio Secretary; (h) one representative, not below the status of an officer of BBPS- 19 [.....], of each of the Ministries of Commerce Industries & Justice to be nominated by the Federal Government; and (i) one representative of the Central Board of Revenue, not below the status of an officer of B-20, to be nominated by the Federal Government; (j) Cost Accountant of the Ministry of Health; (k) One physician, to be nominated by the Federal Government; (j) One Surgeon, to be nominated by the Federal Government. or an officer of the Provincial Health Department not below the status of Additional Secretary, to be nominated by the Secretary, Health Department of that Province. and (m) one expert in veterinary medicine to be nominated by the Federal Government. (2) No person who is a member of the Appellate Board shall be nominated to the Central Licensing Board. (3) The members of the Central licensing Board, other than its ex officio members, shall hold office for three years and shall be eligible for renomination. (4) The Central Licensing Board may co-opt any other person who is expert in the pharmaceutical or medical profession for advice on any particular matter under consideration. (5) The meetings of the Central Licensing Board may be held at such time as the Board may deem fit and, on the request of any of its members, the Chairman may at any time call a meeting if there is any important matter for its consideration. (6) In the absence of the Chairman, the Board may elect one of its members to preside over a meeting. (6-A) The quorum to constitute a meeting of the Board shall be one third of its total membership. (7) The Central Licensing Board may authorise the Chairman to any of its members to perform any specific function of the Board for a specified period. (8) The Central Licensing Board shall follow such policy directing as the Federal Government may issue from time to time. (9) No act or proceeding of the Central Licensing Board shall be invalid merely on the ground of the existence of any vacancy in, or any defect in the constitution of the Board. (10) The chairman and the Secretary of the Central Licensing Board shall, after the Board has approved the issuance of a licence sign the licence. (11) Subject to rule 14, the Central Licensing Board may appoint a licensing authority or authorities for such purpose as it may deem fit. 9. Powers of the Central Licensing Board: (1) The members of the Central Licensing Board shall exercise all the powers of an Inspector without restriction as to area, and shall have the powers of a Provincial Inspector in relation to Section 30. (2) In the exercise of their powers the members of the Central Licensing Board shall follow the procedure prescribed for the Federal Inspector - Provided that member nominated by a Provincial Government may follow the procedure as laid down for a Provincial Inspector. 10. Procedure of Central Licensing Board: (1) The Central Licensing Board may, before issuing a licence, cause the premises in which the manufacture is proposed to be conducted to be inspected by itself or by its sub-committee or by a panel of Inspector or experts appointed by it for the purpose, which may examine all portions of the premises and the plant and appliances, inspect the process of manufacture intended to be employed and the means to be employed for standarizing, if necessary, and analysing substances to be manufactured and enquire into the professional qualifications of the technical staff employed. (2) Where inspection under sub-rule (1) is carried out by a sub-commmittee or panel of experts of Inspectors appointed under the said sub-rule it shall forward to the Central Licensing Board a detailed report of the result of the inspection. (3) If the Central Licensing Board, after' such further enquiry, if any, as it may consider necessary, is satisfied that the requirements of the rules have been complied with, it may issue a licence in Form 2. (4) If the Central Licensing Board is not so satisfied, it shall reject the application and shall inform the applicant of the reasons for such rejection and of the conditions which must be satisfied before a licence may be issued. (5) No application shall be entertained within three months of the rejection of an application under sub-rule (4). (6) If after the expiry of three months but within six months of the rejection of an application under sub-rule (4), the applicant informs the Central Licensing Board that the requirements of the rules have been fulfilled, the Board may if after causing a further inspection to be made, is satisfied that the conditions for the grant of a licence have been complied with, issue a licence and no further fee shall be required to be deposited for such an application. (7) In case an application for licence to manufacture is made after the expiry of six months from the date of rejection of an application under sub-rule (1), such application shall be treated as a fresh application and full fee shall have to be deposited. 11. Special provisions regarding grant of a licence: (1) Where a manufacturer intends to manufacture a drug a part of the process of which is of specialised nature and would be uneconomical for him to conduct it, the Central Licensing Board may permit such process to be undertaken at another licensed premises specialised for this purpose, subject to such conditions, if any, as may be specified in this behalf. (2) If a person is conducting a part of the process of the manufacture on behalf of another manufacturer in accordance with the permission granted under sub-rule (1), and he is not responsible for the quality of the final product, the Central Licensing Board may not require him to establish an independent quality control laboratory for such products. (3) If a person possesses, or applies for, more than one type of licences to manufacture drugs in the same premises, he may establish one Quality Control Department for the purpose of both the licences. 12. Cancellation or suspension of licences: (1) If licensee does not comply with any of the conditions of a licence or violates any of the provisions of the Ordinance or the rules, or fails to deposit the requisite amount of the Central Research Fund due from him, the Central Licensing Board may, by an order in writing stating the reasons thereof, cancel a licence or suspend it for such period as it thinks fit, either wholly or in respect of some of the drugs to which it relates. (2) The Central Licensing Board shall, before cancelling or suspending a licence under sub-rule (1), provide an opportunity of being heard to the licensee. (3) When a licence is cancelled or suspended, an entry to that effect shall be recorded on the licence. (4) A licensee whose licence has been cancelled or suspended may appeal to the Appellate Board within sixty days of the date of receipt of the decision of the Central Licensing Board by the licensee and until the Appellate Board has given its order, the licence shall remain cancelled or suspended, as the case may be. 13. Renewal of a licence: On application being made for renewal, the Central Licensing Board may cause an inspection to be made, and if satisfied that the conditions of the licence and the rules are and will continue to be observed, shall issue a certificate of renewal or otherwise reject the application and inform the licencee accordingly. 14. Licensing authority: For the purpose of Section 18 of the Ordinance the Secretary to the Government of Province in the Health Department shall be the licensing authority for that Province. 15. Conditions for grant or renewal of a licence to manufacture drugs by way of basic or semi-basic manufacture: (1) Before a licence to manufacture by way of basic or semi-basic manufacture is granted or rehewed, the Central Licensing Board shall satisfy itself that the following conditions are complied with by the applicant, namely :-- (a) The applicant shall provide premises which shall be suitable for intended use, in size and construction and shall be located in an area free from offensive and obnoxious odours and other possible sources of contamination. (b) The applicant shall provide adequate space, plant and equipment for the manufacturing operations; (c) The manufacture shall be conducted under the active directions and personal supervision of competent technical staff consisting of. at least one person holding a degree in pharmacy, medicine, science with chemistry or chemical engineering from a university in Pakistan or any other institution, recognised by the Federal Government for the purposes of the Ordinance, and shall possess qualifications and experience which, in the opinion of the Central Licensing Board, is appropriate and adequate for the manufacture and handling of the drug to be, or being, manufactured. (d) The applicant shall establish an independent Quality Control Department and maintain separate staff, premises and adequate laboratory equipment for carrying out tests of the strength, potency, quality and purity of the substances being or to be used in the manufacture. (e) The Quality Control Department shall be independent of the manufacturing units and its incharge shall be a whole-time employee of the manufacturer and shall possess a degree in pharmacy, or a degree in science with chemistry, or a degree in medicine, microbiology, pharmacology, or bacteriology from a university in Pakistan or any other institution recognised by the Federal Government for the purposes of Ordinance, as the Central Licensing Board may deem fit for any particular unit; and shall be independent of the incharge of the manufacture (Production Units). (f) the applicant shall ensure that-- (i) the manufacturing premises shall be maintained propedy and shall, as far as possible, be ordedy, clean and free from accumulated waste and vermin; (ii) unhygienic practices eating and smoking shall not take place in any production or quality control area; (ii) sufficiently clean, appropriately ventilated toilet facilities, including facilities for washing and room for changing clothes, shall be available for the use of manufacturing personnel where required; (iv) hygienic garments shall be worn by all staff in processing and packaging areas; (v) high standard of personnel hygiene shall be observed by all persons concerned with production processes, and (vi) no person known to be suffering from communicable disease or to be a carrier of such a disease and no person with. open lesions or skin infection shall be engaged in production areas. (g) The applicant shall provide-- (i) adequate facilities for first aid; (ii) medical inspection of workers at the time of employment and periodical check up thereafter at least once a year; (iii) facilities for vaccination and inocculation against the enteric or any other epidemic group of diseases; and (iv) adequate precautions for safe-guarding the health of the workers, including measures to avoid industrial accidents or diseases. Provided that where a person possess or applies for a licence to manufacture by way of basic and he also intends to conduct semi-basic manufacture of drugs, he may conduct such manufacture under the same license, subject to the approval of, and under such conditions as, the Central Licensing Board may specify, and 16. Conditions for the grant or renewal of licence to manufacture drugs by way of formulation:Before a licence to manufacture drugs by way of formulation is granted or renewed, the Central Licensing Board shall satisfy itself that the following conditions are being complied with by the applicant namely :-- (a) The factory premises shall comply with the conditions specified in Schedule B. (b) The applicant shall provide adequate space, plant and equipment for the manufacturing operations, the minimum space, plant and equipment for various operations are specified in Schedule B-1. (bb) An applicant for registration of insecticides, pesticides and household disinfectants shall, in addition to the conditions specified in Schedule B and Schedule B-l, comply with the conditions specified in Schedule B-l, A. (c) The manufacture shall be conducted under the 'active directions and personal supervisions of competent technical staff conisting of at least one person who is a whole-time employee and who has-- (i) a degree in Pharmacy from a university in Pakistan or any other institution recognised by the Federal Government for the purpose of the Ordinance and has at least twelve months of practical experience in the manufacture of drugs; or (ii) a degree in science with chemistry or pharmaceutical chemistry as the principal subject who, for the time being is working as incharge of a licensed pharmaceutical manufacturing unit, has not less than ten years practical experience in the manufacture of drugs intended to be manufactured knowledge of pharmacy which, in the opinion of the Central Licensing Board is adequate for the purposes; or (iii) any foreign qualification the quality and content of the training of which are comparable with those described in sub-clause (i) or sub-clause (ii) and is approved for the purposes, of this sub-rule by the Central Licensing Board: Provided that the Central Licensing Board may, in the case of manufacture of drugs included in Schedule C, permit the manufacture of such drugs under the active direction and personal supervision or a person holding a degree in medicine or veterinary sciences of a university in Pakistan or any other institution recognised by the Federal Government, with at least three years experience in the manufacture, testing and analysis of biological products which are intended to be produced: Provided further that the Central Licensing Board, may, in the case of anufacture of disinfectant fluids, insecticides liquid paraffin, medicinal gases, non-chemical contraceptives, plaster of paris, surgical dressing or chemicals for the manufacture of which the knowledge of pharmacy or pharmaceutical chemistry is not essential, permit manufacture of the drug under the active direction and personal supervision of competent staff who, […..] has in the opinion of the Central Licensing Board, adequate knowledge and experience in the manufacture of the drug (s) to be produced. (d) The applicant shall establish an independent Quality Control Department and maintain separate staff, premises and adequate laboratory equipment for carrying out tests of strength, quality and purity of the substances being or to be used in the manufacture. Provided further that a person already approved by the Central Licensing Board as the production incharge of a pharmaceutical firm shall continue to be the technical supervisor of that firm for the purposes of this rule. (e) The Quality Control Department shall be independent of the manufacturing unit and its incharge shall be whole time employee of the manufacturer and shall possess a degree in pharmacy, or a degree in science with chemistry or a degree in medicine or pharmacology (for pharmacological testing) or a degree in microbiology (for microbiological testing) and has sufficient experience in testing of drugs: Provided that in the case of drugs specified in Schedule C, the Central Licensing Board may allow the applicant to make arrangements with some other institution approved by the Central Licensing Board for such tests to be regularly carried out on his behalf by that institution. 17. Licence to manufacture drugs by way of repacking: (1) A licence to manufacture drugs by way of repacking is required for the repacking of such drugs, and under such conditions, as are specified in Schedule D. (2) Where a person possesses or applies for a licence to manufacture by way of formulation and he also intends to conduct repacking of drugs, he may conduct such repacking under the same licence subject to the approval of, and under such conditions as, the Central Licensing Board may specify. 18. Condition for the grant or renewal of a licence to manufacture drugs by way of repacking:Before a licence to manufacture drugs by way of repacking is granted or renewed, the Central Licensing Board shall satisfy itself that the following conditions are complied with by the applicant, namely :-- (a) adequate space and equipment shall be provided; (b) repacking operation shall be carried out under hgygienic conditions and under supervision of technical staff provided for in clause (c) of rule 16; (c) adequate arrangements shall be provided for carrying out the tests for strength potency, quality and purity of the drugs to be repacked. 19. Conditions of licence to manufacture, by way of basic manufacture, semi-basic manufacture formulation and repacking of drugs: (1) A licence to manufacture by way of basic, semi-basic manufacture, formulation or repacking of drugs shall be subject to the conditions stated herein, if any, and to the further condition that the licensee shall continue to maintain conditions on the basis of which he was granted a licence. (2) The licence shall be kept on the licenced premises and shall be produced at the request of any member of the Central Licensing Board or of Provincial Quality Control Board or an Inspector. (3) Any change in the expert staff or significant alteration in the licensed premises or equipment shall be immediately notified to the Central Licensing Board. (4) The licensee shall maintain in the inspection book provided by the Central Licensing Board at the time of the issuance of the licence on which a member of the said Board or of a Provincial Quality Control Board or an Inspector shall record proceedings of each of his visits, his impressions and the defect or irregularities noticed, if any, by him and such inspection book shall be signed by him as well as the licensee or his authorised agent. (5) If any defects or irregularities are recorded in the inspection book under sub-rule (4) the manufacturer shall take steps to remove such defects or irregularities. (6) A licensee who for any purpose is engaged in the culture or manipulation of pathogenic spore bearing micro-organisms shall provide, to the satisfaction of the Central Licensing Board, separate laboratories, utensils and apparatus required for the culture or manipulation of such .micro-organisms, and they shall not be used for the manufacture of any other substance. (7) The licensee shall comply with the provisions of the Ordinance and the rules and with such further requirements, if any, as may be specified in any rule subsequently made-in this behalf or any other condition that may be imposed at the time of grant of a licence in the special circumstances of each case. (8) The licensee shall allow any member of the Central Licensing Board or of a Provincial Quality Control Board or an Inspector to enter, withg or without prior notice, any premises and to inspect the plant and the process of manufacture & the means employed in standardising and testing the drugs and to take samples for test and analysis. (9) The licensee shall allow any member of the Central Licensing "Board or of a Provincial Quality Control Board of an Inspector to inspect all registers and records maintained under these rules and to take samples of the manufactured drugs and shall supply to such member or Inspector such information as he may require for the purpose of ascertaining whether the provisions of the Ordinance and the rules have been observed. (10) The Licensee shall, on demand, furnish to the Central Licensing Board or the Provincial Quality Control Board or to such authority as the Central Licensing Board may direct, from every batch of a drug, or from such batch or batches of drugs as it may from time to time specify, a sample for examination and, if required, furnish full Protocols of the tests which have been applied. (11) If the Central Licensing Board or a Provincial Quality Control Board so directs, the licensee shall not sell or offer for sale any batch of a drug in respect of which a sample is, or protocols are, furnished under clause (10) until a certificate authorising the sale of the batch of such drug has been issued to him by or on behalf of the Central Licensing Board or the Provincial Quality Control Board, as the case may be. (12) The licensee shall on being informed by the Central Licensing Board or a Provincial Quality Control Board that any part of any batch of a drug has been found not to conform with the requirements of the Ordinance or the rules and on being directed so to do, withdraw the remainder of the batch of such drug from sale and, so far as may in the particular circumstances of the case be practicable, recall all issues already made from that batch and dispose it of in such manner as may be directed by the said Board. (13) No drug manufactured under licence shall be sold unless the precautions necessary for preserving its properties have been observed throughout the period after manufacture. (13-A) The licensee or his authorised agent shall issue a warranty in Form 2-A For any drug sold by him for the purpose of re-sale or distribution. (14) The Licensee shall , by the 30th June and the 31st December each year, Whichever is immediately after the annual financial closing of the company. contribute one per cent of his gross profit before deduction of income-tax towards the Central Research Fund to be maintained by the Federal Government and utilised by it in accordance with the Drugs (Research) Rules, 1978: Provided that the Central Licensing Board may aliow a portion of such contribution to be spent by the firm itself for research and development of new drugs or for establishing research laboratories when it is fully satisfied that such expenditure will be utilised for the said purpose effectively and properly. Explanation: In this sub-rule, "profit" means gross profit before payment of income tax or other tax. (14-A) The contributions made towards the Central 'Research Fund under sub-rule (14) shall be kept in such bank as the Federal Government may specify and shall be utilised in accordance with the Drugs (Research) Rules, 1978. (15) The licensee shall, on or before the 31st July each year, submit a duly Signed profit and loss statement as per "PROFORMA" given in FORM-1 of SCHEDULE-A alongwith an evidence of deposit of 1 per cent of profit towards the Central Research Fund; 20. Additional conditions of licence to manufacture drugs by way of formulation: A licence to manufacture drugs by way of formulation shall, in addition to the conditions laid down in rule 19, be subject to the following further conditions, namely :-- (a) The licensee shall comply with the requirements and the conditions in respect of goods practices in the manufacture and quality control of drug; as specified in Schedule B-II. (b) The licensee shall record in Schedule B-Ill the particulars of manufacture of each batch of drugs manufactured by him and shall retain such records, in the case of a substance for which expiry date is fixed for a period of two years from the expiry of such date and, in the case of other substances, for a period of five years from the date of manufacture. (c) The licensee shall either in his own laboratory or, where so authorised under the proviso to clause (e) of rule 16, in any other laboratory approved by the Central Licensing Board, test each batch of the raw materials used by him for the manufacture of drugs and also each batch of the final drug, shall maintain records showing the particulars in respect of such tests as specified in Schedule B-III and shall retain such records, in the case of a substance for which expiry date is fixed for a period of two years from the expiry of such date and, in the case of other substances, for a period of five years from the date of manufacture. 20A. Contract Manufacture.-- Manufacture or analysis on contract is permissible on behalf of a licensee or of a pharmaceutical company whose products are registered in Pakistan for sale subject to the conditions laid down in Schedule G," as a special case and for genuine reasons as approved by the Registration Board. 21. Licence to manufacture drugs for experimental purposes: (1) If a person intending to manufacture a drug for experimental purposes does not hold a licence to manufacture drugs, he shall before commencing such manufacture, apply in Form 3 for the grant or renewal of a licence to the Central Licensing Board addressed to its Secretary. (2) An application under sub-rule (1) shall be countersigned by the head of the institution in which,. or the director or manager of the firm or company by which, the drug will be manufactured. (3) The licence for the manufacture of drugs for experimental purposes shall be in Form 4. 22. Conditions of licence to manufacture drugs for experimental proposes: A licence issuing under rule 21 shall be subject to the following conditions, namely :-- (a) That licensee shall use the drugs manufactured under the licence exclusively for experimental purposes and shall carry on the manufacture and experimental work at the place specified in the licence. (b) The licensee shall allow a member of the Central Licensing Board or of a Provincial Quality Control Board or an Inspector to enter, with or without notice, the premises where the drugs are manufactured and to satisfy himself that the manufacture is being conducted for experimental purposes. (C) The licensee shall comply with such further requirements, if any, as may be specified under any rule subsequently made. 23. Labeling of drugs manufactured for experimental purposes: (l) Any d-rug manufactured for experimental purposes shall be kept in containers bearing labels indicating the purpose for which it has been manufactured. (2) If any drug manufactured for experimental purposes is supplied by the manufacturer to any other person, the container shall bear a label on which shall be stated the name and address of the manufacturer, the accepted scientific name of the drug, if known, or, if not known, a reference which will enable the drug to be identified and the purpose for which it has been manufactured.

CHAPTER 3 REGISTRATION OF DRUGS 24. Registration Board: (1) The Registration Board shall consist of such members, including the Chairman and the Secretary, and its members-shall hold office for such term, as is prescribed for the Central Licensing Board set up under rule 8. (2) The Registration Board may refer any case for detailed .examination to the committee of experts on the Drugs Evaluation constituted under Section 10 of the Act. (3) The Registration Board may appoint a sub-committee consisting of at least one Clinical Professor, one pharmacologist and one pharmacist to make a detailed examination of each case and to submit a report for the consideration of the Board. (4) The Registration Board may appoint a panel of experts or inspectors to inspect on behalf of the Board the premises of a manufacturer of drugs and to submit its report to the Board. (5) The Chairman and the Secretary of the Registration Board shall, after the Board has approved the registration of a drug, sign the certificate of registration. (6) For the manner and conduct of the meetings of the Registration Board, the provisions of sub-rules (3), (4), (5), (6), (7), (8), and (9) of rule 8 shall mutatis mutandis apply. 25. Powers of Registration Board: The members of the Registration Board shall exercise all the powers of Inspector without restriction as the area, and shall have the powers of a Provincial Inspector in relation to Section 30. 26. Application for registration of drugs and fees thereof: (1) An application for registration of a drug shall be made in Form 5 or 5-A in duplicate to the Registration Board addressed to its Secretary, and separate application shall be made for each drug. (2) The applicant shall furnish such further information and material as may be required by the Registration Board for the proper evaluation of the drug. (3) An application under sub-rule (1) shall be accompanied by fee or-- (a) rupees one thousand for the registration of new drug; (b) rupees five hundred for the registration of any other drug; and (c) rupees two hundred and fifty for the renewal of the registration of a new or any other drug: Provided that the application for the renewal of registration is made before the expiry of the validity of the certificate of registration. (3-A) Application for renewal of registration of a drug shall be made in Form 5-B. (3-B) Any application under sub-rule (1) or sub-rule (3) shall be accompanied by the proper fee specified in Schedule F. (4) If the application for renewal of registration is made after the expiry of the period of the validity of the certificate or registration, it shall be treated as a fresh application for the registration of drug. (5) A fee of rupees fifty shall be paid for a duplicate copy of the certificate of registration if the original is defaced, damaged or lost, and such copy of the certificate shall bear the words "Duplicate Copy". (6) Any fee deposited under sub-rule (3)shall in no case be refunded. 27. Duration of certificate of registration: A certificate of registration under this chapter, shall, unless earlier suspended or cancelled, be. in force for a period of five years from the date of Registration of the drug and may thereafter be renewed for periods not exceeding 5 years at a time. Provided that an application for the renewal of registration shall not be entertained unless it has been made within sixty days after the expiry of the registration and when an application has been made as aforesaid the registration shall subject to the orders passed on the application for the renewal continue in force for the next period of five years : Provided further that, if in the opinion of the Registration Board it is necessary so to do in the Public interest, it may provisionally register a [....] drug for period of two years. 28. Certificate of registration: A certificate of registration of drug shall be issued in Form 6. 29. Procedure for registration: (1) The Registration Board may, if it considers necessary, cause the application for registration and the information and material supplied to it under rule 26 to be evaluated by a Committee on Drugs Evaluation consisting of experts related to the aspect of the drug to be evaluated and obtain its report. (2) The Registration (2) The Registration Board may, before issuing a registration], cause the premises in which the manufacture is proposed to be conducted to be inspected by itself or by its sub-committee or by a panel of Inspectors or experts appointed by it for the purpose, which may examine all portions of the premises and the plant and appliances, inspect the process of manufacture intended to be employed and the means to be employed for standardising, if necessary, and testing the substances to be manufactured and enquire into the professional qualifications of the technical staff employed. (3) Where inspection under sub-rule (2) is carried out by a Sub-Committee or panel of experts or Inspectors appointed under the said sub-rule, it shall forward to the Registration Board a detailed report of ;he result of the inspection. (4) If the Registration Board, after such further enquiry, if any, as it may consider necessary, is satisfied of its safety, efficacy, quality and economical value or where the public interest so requires, it may register the drug and issue a certificate of registration in Form 6, subject to such specific conditions as it may specify.' (5) The Registration Board may, while registering a drug under sub-rule (4), approve the details as supplied by the applicant or approve them with amendments as it may deem fit in respect of the following particulars, namely :-- (a) the name under which the drug may be sold; (b) the labelling; (c) the statement of all the representations to be made for the promotion of the drug in respect of-- (i) the claims to be made for the drug; (ii) the route of administration; (iii) the dosage; (iv) the contra-indications, the side effects and precautions if any; and (d) Omitted by S.R.O. 551(1)//93, dated 3. 7. 1993. (5-A) Where the Registration Board registers a new drug, it may recommend to the Federal Government for fixation of maximum price of such drug. (6) The Registration Board shall, before registering a new drug for which the research work has been conducted in other countries and its efficacy, safety and quality has been established therein, require the investigation on such pharmaceutical, pharmacological and other aspects, to be conducted and clinical trials to be made as are necessary to establish its quality and, where applicable, the biological, availability, and its safety and efficacy to be established under the local conditions: Provided that under special circumstances to be recorded in writing, the Registration Board may register a drug and require such investigations and clinical trials to be conducted after its registration. (7) A new drug, where new method of manufacture is contemplated or a change is proposed in source, standard or specification of the active ingredient or the finished product, may not require full investigations and clinical trials except in so far as they are necessary for the purpose of establishing bio-equivalence, absorption, acceptability or other such features. (8) Where it is necessary in the public interest so to do, the Registration Board may register a drug on its own motion without having received any application for registration. (9) If the Registration Board is not satisfied as to the safety, efficacy, quality or economic value of a drug, or where the public interest so requires it may, [ .]..., reject the application for registration and inform the applicant of the reasons for such rejection in writing. (10) Rejection of an application for the registration of a drug shall not debar an applicant from submitting a fresh application under rule 26. 30. Conditions or registration of drug: (1) The relevant provisions of the Ordinance and the rules in respect of the registered drug, shall be complied with. (2) The import, manufacture and sale of drugs shall be in accordance with the information contained in the applications in respect of those drugs or in any supplementary information or, where such information was amended by the Registration Board, in accordance with such amended information on the basis of which such drugs were registered: Provided that deviations from any such information may be made only after obtaining prior approval of the Registration Board. (3) The indications, contra-indication, side effects, the dosage and cautions, if any, as have been approved for the purpose of registration of a drug shall be clearly specified in the labelling and promotion. (4) Every drug shall be produced in sufficient quantity so as to ensure its regular and adequate supply in the market. (5) The manufacture of any drug shall not, without the prior approval of the Registration Board, be discontinued for period which may result in its shortage: Provided that in the circumstances beyond the control of a manufacturer,, of a drug which may lead to reduction in the production of that drug, the circumstances may be intimated to the Registration Board. (6) A record of quarterly production and disposal of a drug shall be maintained and supplied to the Chairman of the Registration Board in Form 7 in the months of January, April, July and October each year. (7) In case of an imported drug, the indenter or any other approved representative in Pakistan of the foreign firm shall ensure regular and adequate supply of tee drug in Pakistan. (7-A) The indenter, importer or manufacturer's authorised agent shall issue a warranty in Form 2-A for any drug indented or sold by him for the purpose of re-sale or distribution; and (8) In respect of new drug, records, including adequately organised and indexed files, shall be maintained containing full information regarding-- (a) animal or clinical investigations and tests conducted by the manufacturer or reported to him by any person concerning that drug; (b) reports from the scientific literature or the bibliography therefrom that are available to him concerning that drug; (c) experiences, investigations, studies and tests involving the chemical or physical properties or any other properties of that drug; (d) any substitution of another substance for that drug or any mixing of another substance with that drug; (e) any error in the labelling of that drug; (f) any bacteriological or any significant chemical or physical or other change or deterioration in any batch of that drug; (g) any failure of one or more distributed batches of that drug to meet the required specifications; (h) any unexpected side effects, injury, toxicity or sensitivity reaction associated with the clinical uses, studies, investigations and tests respecting that drug; and (i) any unusual failure of that drug to product it expected pharmacological activity. (9) The following information shall be supplied to the Registration Board-- (a) on request, report in duplicate of all records respecting the information contemplated by paragraphs (d), (e), and (f) of sub-rule (8); and (b) immediately upon receipt by him, reports in duplicate of all records respecting the information contemplated by paragraphs (d), (e) and (f) of sub-rule (8); and (c) as soon as possible and in any event within fifteen working days of their receipt by him, reports in duplicate of all records respecting the information contemplated by paragraphs (g), (h) and (i) of sub-rule (8). (10) If a drug or any of its ingredients, which is imported or manufactured by a company in Pakistan is also approved for registration and free sale by its subsidiary, sister concern, associate or parent company in the country where it was originally developed or in any of the countries namely, USA, European Union Countries, Canada, Japan, Australia, and-- (a) if that drug at any time, for safety reasons is withdrawn or banned or certain restrictions are imposed in any of the said countries, then it shall be the responsibility of the manufacturer in Pakistan or as the case may be, the indentor, to immediately withdraw the drug from the market in Pakistan or, as the case may be to impose similar restriction and to inform the registration Board within fourteen days of such an information having come to his knowledge and haviong taken the necessary action. The Registration Board after getting the said intimation shall take similar action for the same drug available from other sources within the shortest possible time; (b) if a climical information for a drug is approved by the Drug Regulatory Authority in any of the said countries, the same clinical information shall be considered as approved for drug registration in Pakistan unless modified by the Registration Board on the basis of scientific data available to it, and such clinical information may include indication, contra-indications, side effects, precautions, dosage, etc; (c) if any adverse drug reaction not otherwise included in the application for registration, is registration, is registered in any of the said countries, it shall be the responsibility of the concerned manufacturer or in case of imported drugs the indentor or manufacturer's agent in Pakistan, to be aware of such adverse action and to report to the Registration Board within thirty days of becoming so aware. (11) The manufacturer or as the case may be, the indentor shall follow the ethical criteria for medical drug promotion as given in Schedule G. (12) The manufacturer or, as the case may be, the indentor shall supply the information in relation to safety, efficacy, production, quality, or availability of the drugs as and when required by the Registration Board with a view to ensure safety, efficacy or quality of the drug

CHAPTER IV ADVERTISING OF DRUGS, Etc. 31. Conditions for Advertising: (1) The Federal Government may, after seeking advice of the Committee on Advertising, allow the advertisement of a drug, or any substance or a remedy as specified in Schedule D-1 or a treatment or offer of a treatment for any disease. approve the contents of such advertisement and specify conditions subject to which such advertisement shall be made: Provided that the Federal Government may, if in its opinion the public interest so required, withdraw the approval granted to any advertisement or modify or alter any condition subject to which the advertisement was approved. (1-A) An application for advertisement of any drug, substance, remdy, treatment or offer of treatment for any disease shall be made it Form-8, addressed to the Secretary of the Commissioner on Advertising and there shal be made a separate application for each advertisement. (l-B) An application under sub-rule (l-A) shall be accompanied by the proper fee specified in Schedule F : and (1-C) The approval of the advertisement, granted under sub-rule (1), shall be valid for a period of two years only. (2) A drug or any substance referred to in clause (ii) of Sec. 24 may be advertised to the medical, pharmaceutical and allied professions, without referring to the Federal Government, through medical representatives or through professional journals and publication which are meant for circulation exclusively amongst the members of the medical, pharmaceutical and allied professions · Provided that: (i)one copy of each issue of such journal or publication is sent to the Drug Administration of the Health Division; and (ii) the Federal Government may, after giving an opportunity of being heard, prohibit the publication of any advertisement in any such journal as it is found to violate any of the conditions specified under sub-rule (1). (3) Advertisements under sub-rule (2) shall be subjected to the following conditions, namely :-- (i)All claims shall be made in accordance with these approved for registration of that drug. (ii) Where the usual information on indications and dosage is provided, that advertisement material shall contain information on contra-indications, side effects and other necessary precautions as may be applicable. (4) A drug or any substance referred to in clause (ii) of Section 24, may be advertised through Press without reference to the Federal Government if it is merely intended to inform the public of the availability or the price of such drug or any substance referred to in clause (ii) of Section 24 subject to the condition that the Federal Government may prohibit such advertisement if, in its opinion, the public interest so requires. (5) A drug or any substance referred to in clause (ii) of Section 24, may be advertised to the medical, pharmaceutical and allied professions through a documentary film. (6) No advertisement under this rule shall contain any direct or indirect comparison in any way with any other drug or substance or remedy for any disease for the purpose of attracting customers or with a view to discredit other such product. (7) Advertisement material shall be presented with courtesy and good taste and words and phrases implying urgency, uniqueness or such expressions which are absolute in character, such as "the most potent", "the most rapid", "the most efficacious", or which make exaggerated claims or to general claims, such as "effective in all cases" or "effective against all complaints" or superlatives shall be avoided. (8) Advertisement of a drug or any substance referred to in clause (ii) of Section 24 shall include such information or any risks and other precautions as may be necessary for the protection of public health, and in the case of drug also its maximum retail price fixed under Section 12. (9) No drug or any other substance shall be advertised in a manner which encourages self-medication or use to the extent that it endangers health. (10) No drug or any remedy, treatment or after treatment of any disease specified in Schedule 'E' shall be advertised except as provided in sub-rule (2). (11) Reminder publications for the medical, pharmaceutical and allied professions shall include the name of the drug and its exact composition, the price, the name and address of the manufacturer and a statement to the effect that "Full information is available on request". 32. Sampling of drugs: Samples of drugs may be provided to the physicians or dentists or Pharmacists or Veterinarians or a medical institution in a reasonable quantity and in reduced packings marked with the words "Physicians Sample Not for Sale". 33. Expenditure on advertisement: No person shall spend more than five per cent of his turnover on advertisement, sampling and other promotional activities in respect of drugs, Explanation: The expenditure on pay and allowances of the field force connected with the promotional activities shall not be included in expenditure for the purpose of this rule. 34. Substances required to be prescribed under Section 24: Any substance or a mixture of substances offered for sale which is injurious, or likely to become hazardous, to the health of a person shall be deemed to be a substance for the purpose of Section 24 of the Ordinance. 35. Retailer's discount: The retailers discount shall be 15% of the maximum retail price.

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