Improving Quality of drugs & regulatory controls in India

                                  -      Ganadhish Kamat

 

 

As per the Drugs and Cosmetics act 1940, Central Drugs Standard Control Organization (CDSCO) is the highest drug regulatory body of India headed by Drugs Controller General of India.

The Vision of CDSCO is “To protect and promote public health in India” whereas the mission is defined as “To safeguard and enhance the public health by assuring the safety, efficacy and Quality of the drugs, cosmetics and medical devices. The strategies have been listed as follows –

1.       Initiate in framing of rules, regulations and guidance documents to match the contemporary issues in compliance with the requirements of Drugs & Cosmetics Act 1940 and Rules 1945.

2.       Facilitate in uniform implementation of the provisions of the Drugs & Cosmetics Act 1940 and Rules 1945.

3.       Function as Central license Approving Authority under the provisions of Drugs and Cosmetics Act 1940 and Rules 1945.

4.       Collaboration with other similar international agencies.

5.       Providing training to the Indian regulatory personnel.

Under the Drug and Cosmetics Act, the CDSCO is responsible for approval of New Drugs, Clinical Trials in the country, laying down the standards for Drugs, control over the quality of imported Drugs, coordination of the activities of State Drug Control Organisations and providing expert advice with a view to bring about uniformity in the enforcement of the Drugs and Cosmetics Act.

CDSCO is also responsible for approval of licenses of specified categories of Drugs such as blood and blood products, I. V. Fluids, Vaccine and Sera.

The regulation of manufacture, sale and distribution of Drugs is primarily the responsibility of the State authorities.

If one looks at the websites of any regulatory agencies like USFDA, MHRA, TGA etc, one will find organization chart clearly showing how the responsibilities are distributed across the functions or departments. This type of organization chart is however missing on CDSCO website. Website does have “Who’s who” list which has names of senior people with their designations without mentioning their functional responsibility. This is not in line with ‘Values’ of transparency, accountability, punctuality, courtesy, openness, responsiveness, professionalism, impartiality, consistency, integrity and truthfulness defined by CDSCO on their website. The organogram should be modified to show functional responsibilities to make it easy for people to approach right person.

Second Chapter in the Drugs and Cosmetics act describes Drugs Technical Advisory Board (DTAB), The Central Drugs Laboratory and Drugs Consultative Committee. Having featured in the second chapter, DTAB appears to be another most important technical body under the Act and is constituted to advise the Central Government and the State Governments on technical matters arising out of the administration of Drugs & Cosmetics Act and carry out functions assigned to it by this Act. 

Drugs Technical Advisory Board is composed of following members - 

1.       Director General of Health Services, ex officio, (Chairman);

2.       Drugs Controller, India, ex officio.

3.       Director of the Central Drugs Laboratory, Calcutta, ex officio.

4.       Director of the Central Research Institute, Kasauli, ex officio. 

5.       Director of Indian Veterinary Research Institute, Izatnagar, ex officio.

6.       President of Medical Council of India, ex officio.

7.       President of the Pharmacy Council of India, ex officio.

8.       Director of Central Drug Research Institute, Lucknow, ex officio.

9.       Two persons to be nominated by the Central Government from among persons who are in charge of drugs control in the States;

10.   One person, to be elected by the Executive Committee of the Pharmacy Council of India, from among teachers in pharmacy or pharmaceutical chemistry or pharmacognosy on the staff of an Indian university or a college affiliated thereto;

11.   One person, to be elected by the Executive Committee of the Medical Council of India, from among teachers in medicine or therapeutics on the staff of an Indian university or a college affiliated thereto;

12.   One person to be nominated by the Central Government from the pharmaceutical industry;

13.   One pharmacologist to be elected by the Governing Body of the Indian Council of Medical Research;

14.   One person to be elected by the Central Council of the Indian Medical Association;

15.   One person to be elected by the Council of the Indian Pharmaceutical Association;

16.   Two persons holding the appointment of Government Analyst under this Act, to be nominated by the Central Government.

While the D&C act itself does not clearly define the functions of Drugs Technical Advisory Board, based on the functions listed under DTAB-DCC section under CDSCO, it appears that DTAB is responsible for the approval of amendments in the Drugs and Cosmetics Rules, 1945 apart from deciding on other technical issues.

Pharmaceutical Industry has been making numerous representations to CDSCO and MOH to bring changes in D&C act 1940 and Rules 1945 in line with global regulations to improve the controls and to eliminate bureaucratic processes in the current system which while creating difficulties to the manufacturers, do not provide any benefits to the patients. Since majority of the DTAB members are not from industry or with industry background, they are not likely to have any appreciation of the difficulties being faced by the industry. Most of them are also not likely to have any exposure to global regulatory standards due to their background. This will severely limit their ability to drive the changes required to improve the quality and safety of the drugs distributed in India or even agree with the proposed changes. As per the above list one member has to be elected by Council of Indian Pharmaceutical association. IPA may have been only association in existence at the time when the drug Act was enacted. Now with many associations in place it does not make sense to include members from one association and ignoring others. Only one person is nominated by the central government from the industry on this board. Looking at the past nominees it appears that government nominates CMDs of Pharmaceutical companies instead of nominating technical people although this is supposed to be “Technical advisory board”. Since the composition of the board is flawed, it is essential to bring change in the Act to involve people with right technical background (R&D, Manufacturing, Quality, Supply chain, Academia, Medical field etc) who can add value to the process.

Alternatively, this Board should be scrapped and CDSCO should be strengthened by creating proper organization structure and by inducting right experts from the fields like Medicinal chemistry, Analytical chemistry, Pharmacology, Pharmaceutics, CMC, Clinical research, Pharmaceutical Operations etc to decide on various technical aspects.

 One of the strategies of CDSCO as mentioned on the website is “Facilitate in Uniform implementation of the provisions of the Drugs & Cosmetics Act 1940 and Rules 1945”. If the process followed for grant of drug manufacturing licenses for branded generics and generics in different states is compared, it is evident that this strategy is not getting implemented. Given below is table to compare the documents required for obtaining manufacturing licence in different states.

Documents required	AP	TS	MH	Guj	MP	HP	J&K	Sikkim
Cover Letter	Y	Y	N	Y	N	Y	Y	Y
Form 24/27	Y	Y	N	Y	Y	Y	Y	Y
Challan/Fees	Y	Y	Y	Y	Y	Y	Y	Y
Copy of approval status from DCG(I)/IP 2010/M&M permission	Y	Y	Y	Y	Y	Y	Y	Y
Copy of valid manufacturing licence	Y	Y	N	N	N	Y	Y	Y
Copy of valid GMP certificate	Y	Y	N	N	N	*	N	N
Composition (unit dose)	Y	Y	Y	N	N	*	N	N
Brief manufacturing process and flow chart	Y	Y	N	Y	Y	*	N	N
Specifications and method of analysis of raw materials	Y	Y	N	N	N	*	N	N
Specifications and method of analysis of Finished product	Y	Y	Y	Y	Y	*	N	N
List of equipment (Both QC and Manufacturing)	Y	Y	N	N	N	*	N	N
Draft specimen label	Y	Y	Y	Y	N	*	Y	Y
List of technical staff	Y	Y	N	N	N	*	N	N
Consent letters of technical staff and copies of their approvals (1 QC and 1 manufacturing chemist)	Y	Y	N	N	N	*	N	N
Stability Data with valid T license copy	Y	Y	Y	N	Y	*	Y	N
Copy of authorization letter	Y	Y	N	Y	N	Y	N	N
Production block Details	Y	N	N	N	N	N	N	N

* To be provided only if requested.

Apart from the lack of uniformity in the requirements for documents to be submitted to seek product permission, the list of documents indicate that there is very little technical evaluation done at the time of granting the manufacturing license. For instance, most important documents which are required to be reviewed to assure quality, efficacy & safety of the product, namely the product development report, analytical method validation reports, justification of specification, BA/BE study report etc are not part of requirement in any of the states. Although 9^th amendment to D&C rules dated 3^rd April 2017, made it mandatory to submit BE results for BCS class II & IV drugs, same has not been implemented in most states. For the products which are not official in Pharmacopoeia, the manufacturer can get away by setting their own specifications which may not be in line with ICH requirements. It is not mandatory to include important tests such as dissolution for solid oral dosage forms and test for related substances and residual solvents (for the products where solvents are used in the formulation). Since it is allowed to have shelf life limit of not less than 90% of label claim for the drug content, the product may show degradation as high as 10% and still meet the specification. The degradation products formed may produce adverse effects if not controlled under established safety limits. In absence of BA/BE study showing that the drug product is bioequivalent to Innovator product or Reference Listed Drug there is no guarantee that the product will produce same effect as seen in the clinical trials.

These requirements have become mandatory in every country over the world except in India. If product permissions are granted without assessment of such scientific data, how can the mission of CDSCO of assuring the safety, efficacy and quality of the drugs be achieved?

Quality, safety and efficacy of the products cannot be assured by mere testing but same has to be built into the product during design and ensured through appropriate controls in procurement, processing and distribution. Many responsible companies in India follow global standards for the drugs distributed by them in India because of their own internal Quality systems even though it is not required by law. However, since this is not mandated by the law, large number of manufacturers especially those manufacturing so called generic medicines, don’t follow these standards there by distributing drugs not proven to be safe and effective, at lower cost. Unsuspecting healthcare givers and patients who are not familiar with all these complexities, may consume these unsafe medicines because drug content mentioned on the labels is identical.

To ensure that Indian population gets right quality medicines, there is urgent need to align our drug approval process to global standards. To do this it is necessary to bring appropriate changes in the D&C act and the rules and the way Central and state regulatory agencies are functioning.