National government-run laboratories are responsible for approving the availability of new drugs in the market. Yet, very few of them are NABL-accredited and many of the non-accredited ones fall way below the global standards. There is an urgent need to improve these labs with qualified staff and technical assistance which is lacking as of now, to prod them on the way to progress By Usha Sharma
The Indian pharmaceutical industry is the leader in supplying affordable generic medicines to the world. It has got the highest number of US FDA approved manufacturing facilities outside the US which highlights its capability to deliver affordable healthcare to many nations.
Commenting on the capabilities of Indian pharma companies, SD Joag, Ex Secretary General, Indian Pharmaceutical Association says, “India is the largest producer of essential medicines for management of high-burden diseases in developing countries and speciality drugs to developed countries, both in terms of finished formulations and active pharmaceutical ingredients (APIs). However, the quality of medicines produced in India is frequently under scrutiny the US FDA, UK MHRA, ECA, TGA and WHO will always remain keen to monitor the consistency of quality medicines and regulatory compliance of Indian pharma manufacturers while producing the medicines.”
For the last one and half years, Indian pharma companies have increasingly been pulled up on for the quality front from different countries’ regulators. There have been an increase in warning letters and 483’s, which impacted the pharma export largely. Dr Ajit Dangi, President and Chief Executive Officer, Danssen Consulting mentions, “While India has acquired the distinction of being a reliable source of quality medicines at affordable prices, we have a long way to go as far as consistently producing acceptable quality medicines as shown by the US FDA import alerts and 483s for over dozen large Indian pharma companies in the last few years.”
Explaining the root cause for such an alarming stage and underlying the need for qualified laboratory system in India, Dangi attributes, “The US FDA laboratory forms the back bone of any drug quality issue which the drug manufacturer face. These labs, with few exceptions, more often than not, lack adequate number of trained analysts, sophisticated analytical instruments and accreditation from organisations like National Accreditation Board for Testing and Calibration of Laboratories (NABL). Another important issue is that of data integrity of results produced in such labs.”
Criticality of NSQ drugs
Globally, the Indian pharma industry has shown a tremendous growth and has been recognised as ‘Pharmacy of the World’ but the regulatory agencies in the country have not been able to keep pace with this progress. For several reasons, India is being questioned for its quality. Is it because there is a lack of understanding related to the process or is there other reasons?
The Drugs Act (Amendment) 2008 defines only three categories of drugs under section 36AC namely. spurious, misbranded and adulterated. Dangi informs, “The lack of proper definition for not of standard quality (NSQ) drugs often results in genuine and licensed manufacturers being penalised under the above three categories. Quite often, a standard quality drug manufactured by a licensed manufacturer fails in potency or physical appearance (discoloration, chipped tablets etc. ) due to improper storage or poor supply chain during distribution.” (For more details on NSQ drugs, see story http://www.expressbpd.com/article/pharma/management-pharma/redefining-nsq/89009/)
Dr Raman Mohan Singh, Director, Central Drugs Testing Laboratory, Mumbai, Ministry of Health and Family Welfare, Government of India says, “Analysing the criticality of the issue, the Department of Health, Ministry of Health and Family Welfare decided to define NSQ drugs and proposed necessary changes in Section 36AC. The government has formed a committee under the leadership of Dr Surinder Singh, Former DCGI. Across the country, more than 45,000 samples were collected for assessing and measuring the quality and assigned to six central and two state level laboratories namely Central Drugs Testing Laboratories (CDTL) in Chennai, Kolkata, Kasauli, Regional Drug Testing Laboratories in Chandigarh, Guwahati, Hyderabad and state laboratories in Maharashtra and Gujarat respectively.”
Initially, the committee planned to conduct the tests in private as well as government-run laboratories which are NABL accredited. Singh further says, “The committee decided to accomplish the NSQ project in three to four months through tender process. However, when the quality analysis of those private NABL accredited labs was carried out in , the committee realised that certain required parameters not being followed and hence decided to do all the tests in the central and state-run laboratories. We have received 5000 samples which will be submitted before the end of this year besides our routine tests. Earlier, we used to conduct 2500-3000 tests in a year, which has been doubled now.”
He informs that two months backs the Indian Pharmacopoeia Laboratory (IPL), Ghaziabad, had received the WHO pre-qualified QCL certification which is the first government laboratory which has obtained this certification.
Following the steps of IPL, Singh is gearing up for the Mumbai lab as well. Presently, the CDTL, Mumbai is conducting tests of various samples like import / export samples from airports / port trusts, registration samples, new drugs samples from DCG(I) office, Zonal Survey samples from Zonal and Sub Zonal office of CDSCO, legal samples (Form 18) through central drug inspector, medical devices samples, proficiency testing samples, CGHS samples and other miscellaneous samples. He informs that presently the lab received more than 5,200 samples under drugs survey for drugs safety India through NIB, Noida under the directions of Ministry Health & Family Welfare through CDSCO for checking the NSQ / spurious drugs moving in the country. The analysis of these samples is going on simultaneously with war footing on time bound manner. Singh informs, that “We are in the process of applying NABL accreditation and later we will go for the WHO pre-qualified QCL certification in CDTL, Mumbai.
Singh while replying as to how such accreditation and recognition will be beneficial to the industry says, “With the NABL (ISO / IEC 17025:2005) accreditation, we will be in a position to call our lab a globally recognised one which will assure all quality measures.”
TS Jaishankar, Managing Director, Quest Life Sciences shares his insights and says, “The Tamil Nadu government undertakes regularly testing of samples out of every supply made to pharma medical stores. The major concern of the government laboratories is its ability to handle the volume of work in their respective states. This leads to too many samples waiting for analysis and thereby incapacitating inadequate storage archival and documentation.”
Approaching global standards
In order to meet the global regulatory requirements, the Central Drugs Standard Control Organisation (CDSCO), a national regulatory authority is striving to equip its personnel and systems as per the global standards. The Indian regulatory body had announced to conducted several workshops to train/ update their drug regulators in collaboration with the US FDA, Gujarat FDCA with UL.
According to an industry source, Drug Information Association (DIA) conducts an annual meeting of their worldwide members for a minimum of three days in one of the major cities in the US. Members who take part in the meeting are normally from academia, companies, regulatory bodies and pharmacy students. It is an accepted body of a neutral status and thus provides a neutral platform for all the regulatory experts from various countries to interact and exchange views on regulatory advancements on the global front. It is invariably attended by US FDA, EDQM, EMA and other regulatory authorities of various countries who mingle with these prominent people and exchange ideas and update themselves every year.
The source informs that unfortunately Indian regulators do not seem to be present in numbers. More so, we have not seen any decision maker participating in this international forum except for India programmes. Hence, a good number of opportunities are lost scaling up the knowledge and utilise useful decisions for the countries’ regulatory system. As a result there is big void which exists in terms of the actual methodical regulatory requirements. This is seen and felt conspicuously in our regulatory personnel.
The source also informs that, one gets exposed to various training modules available at these fora which could be used to train regulatory officials. Several small meetings were held on these training areas by WHO authorities along with European Pharmacopoea Authories (EDQM) and EMA. In fact these global regulatory authorities have been suggesting that Indian pharma associations should provide modules for training wherein these authorities will pitch in their expertise.
Singh answers on set expectations from Indian regulators as well as international bodies, and says, “In present scenario, I have not seen such activities where we have exchanged technical assistance in the global sphere. If we do not get the training and exchange programme globally which is being expected, then how are we going to strengthen our parameters and be at par with global standards to recoginise our facilities internationally?”
“Most of the government state-run laboratories are only conducting primary tests in labs and do not have high-end sophisticated instruments required for critical analysis. There is hardly any interaction between the government and industry-run laboratories which results in lack of awareness on GLP practices. Since laboratories have to decide on the end results, the government should ensure primarily that all the state-run laboratories are accredited for GLP by NABL or equivalent or even higher international regulatory bodies,” says Jaishankar.
Dangi reciprocates, “The Maggi episode has opened a Pandora’s Box on the status of government laboratories and their working techniques. While the primary responsibility of producing good quality medicines consistently lies with the manufacturer, regulatory bodies like the FDA need to provide stringent oversight to guard the public health.”
Joag emphasises, “The drug testing laboratories should also be supported with the provision of reference standards at affordable price. The Indian pharma industry is totally dependent on USP/ BP/ EP reference standards which are very expensive. There is enough expertise and talent in our country to produce these reference drug standards or impurity standards. The Indian government should exploit this possibility to support the pharma industry. The API industry and the government will have to work hand in hand for achieving this need.”
Joag further says, “The government should also recognise the need of sophisticated instruments for the evaluation of quality compliance. These instruments are not produced in our country and hence compelled to import these by paying huge money. The regulatory quality requirements are changing fast and upgrading of instruments to meet such requirements is inevitable. The government can support the industry by giving exemption on taxes as the conversion of foreign currency is always on the upsurge.”
Joag says, “However, states like Gujarat, Karnataka and Maharashtra are equipped themselves as per global standards. Dangi highlights, “Food and Drugs Control Administration (FDCA), Government of Gujarat under the able leadership of FDCA Commissioner, Dr Hemant Koshia, has made commendable strides in upgrading the entire administration collaborating with CDSCO, US FDA and US-based training organisation UL. FDCA in Gujarat has a well equipped mobile laboratory to check on counterfeit drugs is a unique initiative. We need more and more FDA labs in the country to emulate FDCA in Gujarat. The need of the day is to have skilled regulators understanding the global requirements of quality compliance in terms of purity, efficacy and safety of drugs and the drug testing laboratories equipped with not only sophisticated instruments but with skilled operators.”
Joag feels, “A capacity building programme for GMP inspectorates and control laboratories should be drawn up, aimed at establishing quality management systems and building staff competence to operate at all international standards. The focus will be on supervisory activities (inspection and laboratory testing) related to the manufacture and quality control of drugs and formulations. Attention should be specifically paid to generic medicines. The capacity building programme should be a regular activity of the CDSCO and state drug control authorities. At the end of every such programmes, the performance should be checked with international standards by informal audits.”
Joag suggests, “The programme could be made mandatory to all drug control departments in India and the drug testing laboratories for strengthening the skill development infrastructure at both inspection and analytical levels. Aimed at empowering the drug regulators and the analysts working in drug testing laboratories with similar regulatory knowledge and analytical skills as offered to the US FDA officials, the CDSCO should soon equip its drug inspectors with relevant areas of current Good Manufacturing Practices (cGMP) through online training or skill development workshops.”
Dangi says, “Many FDA laboratories which have reasonable amount of sophisticated analytical instruments find maintenance and calibration as major problems. Since these instruments have a working life of about five to seven years, availability of spares, after sales service after the guarantee period is over is quite a challenge. It is not the funding which is always the problem. Under the World Bank’s capacity building programme, funds to upgrade such labs are available.”
Indian pharma companies are facing a dual problem in not maintaining a quality-driven process as well as keeping records. Joag opines, “It has also been observed that the foreign regulators are more conscious about documentation and data integrity while auditing the manufacturing units in India. Moreover, the current complex system of drug regulation is unable to provide users with sufficient assurance that the medicines produced comply with international pharma standards and have issued warning letters even to the leading and multinational Indian companies. Is it not an alarming situation?”
Joag highlights, “Compliance with good manufacturing practice and qualified laboratory testing are essential for the production of quality medicines and independent control. The improved performance of GMP inspectors and official drug control laboratories in India could therefore make a significant contribution to verify the quality of medicines, irrespective of whether these are intended for export or for domestic use.”
Joag concludes and says that the quality of medicines produced in India and the reliability of its system for supervision of manufacturers are of great interest to the global regulatory and public health communities. It is therefore considered that the project will be able to elicit support from many regulatory authorities. The need of the hour is therefore to strengthen the capacity of selected GMP inspectorates and medicines testing laboratories in India to enable them to meet international standards.
Jaishankar suggests, “Government laboratories should be accessible to all tier-II and tier-III cities of each state as well.”