After a few falls starts and delays, India’s pharmacopeia is finally being updated and harmonised with global norms. By Sachin Jagdale
In a welcome move, Indian Pharmacopoeia Commission (IPC), along with the health ministry, has initiated interactions with key global pharmacopoeias. This step is expected to help strengthen and harmonise Indian pharmacopoeia standards. Harmonisation of Indian pharmacopoeia (IP) will help the Indian pharmaceutical industry achieve its dream of being a global pharma power.
Need for harmonisation
Despite being third largest in volume, the Indian pharma industry has time and again found itself embroiled in quality-related issues. In recent times, overseas regulatory authorities have issued warning letters to some major Indian pharma companies for lack of adherence with regulatory norms. Standardisation of quality and tests will help resolve this problem to a considerable extent.
A US Pharmacopoeia (USP) spokesperson also stresses on the necessity for harmonisation of standards. He says, “Standards facilitate registration, market surveillance, free movement and trade of medicines among countries. Globalisation and expansion in international trade present a growing need to develop global quality standards for medicines. Public standards are an integral part of the global medicine public safety net that protects patients and helps ensures access to quality medicines. Public quality standards for medicines protect patients and consumers, increase practitioners’ confidence in the quality of medicine, provide benchmarking tools and predictability to industry, and safeguard the integrity of the supply chain, helping to ensure patients’ access to quality medicines. Harmonisation is the process through collaborative effort where by differing requirements among participating’ authorities’ move towards alignment on common requirements that yield the same outcome.”
Dr Vinay Nayak, Executive Director, Marksans Pharma, echoes USP spokesperson’s views and stresses on the need for Indian pharmacopoeia’s standards. He says, “India is a major player in the supply of medicines. Pharma is the sunrise industry in India. Now many pharma companies are showing significant interest in exports. There are three major markets- regulated (Europe, the US and Japan), Latin America and Rest Of the World (ROW) market. So if we have to compete with MNCs in these markets then the quality standards should also match with them. The method of testing should also be on par with USP and British Pharmacopoeia (BP). So harmonisation of standards is necessary.”
It is evident that there is no option for Indian pharma companies but to match international quality standards to achieve their global ambitions. Collection of standards in any pharmacopoeia is legally binding. So, if Indian pharma companies want to tap world’s largest medicine markets like the US, they cannot afford to be lax where quality is concerned and would need to adopt measures for constant quality upgradation.
Dr Suresh Saravdekar, Clinical Pharmacologist and Secretary-Hospital Division, Indian Pharmaceutical Association (IPA) explains, “All the drugs are invented by a few developed countries, mainly from Europe, North America, Japan etc. Consequently, all the standards are developed by the pharmacopoeias of these countries. Rest of the countries form their pharmacopoeias on similar lines. However, developed countries are well aware of the fact that quality is an evolutionary concept and hence needs to be continuously upgraded. So, these countries do continuous research and upgrade the standards in their pharmacopoeias so that good and latest quality standard medicines are made available to their population.” He recommends that Indian pharmacopoeia should also adopt similar measures to be at par with global standards.
He criticises the complacent approach of some of the countries towards harmonisation by saying that, “This updating is not done regularly by rest of the countries who had copied their pharmacopoeias long back from either European/ US/ BP pharmacopoeias etc. Today, these countries are thinking of updating pharmacopoeia under the name of harmonisation.”
A late beginner
According to industry experts, though harmonisation efforts have been underway for some time, India took considerable time to get the ball rolling. So, what caused the delay?
A major reason is that Indian pharma industry didn’t bother about the exports as the focus was on domestic market. As a majority of the pharma industry was content with domestic business, even the government took its time to go ahead with harmonisation of IP. However, with Indian pharma companies exploring the overseas markets and the country’s growth as a generics medicines supplier the need for IP harmonisation also gained urgency.
Kapil Bhargava, Former Dy Drugs Controller (I) CDSCO says, “I feel the harmonisation process started quite late. Historically, IP was adopting monographs from other pharmacopoeias (mostly BP) as such and those standards were accepted. These monographs were mainly of APIs. We started producing a number of APIs ourselves in late eighties, so the content of monographs became more pertinent, especially for impurities and their profiling. Indian manufacturers started producing IP as well as BP/ USP quality materials as standards were different in these pharmacopoeias. After exports from India increased, good API manufacturers realised the importance of monographs and started producing only one quality material conforming to IP/ BP/ USP (which made good business sense too).”
He adds, “You will also notice that a few monographs of IP were ditto of that appearing in other foreign pharmacopoeias and this must have been done to bring about harmonisation of pharmacopoeias. Secondly, around the same time IPC came into existence, scientific body and its director assumed more authority for monograph contents and harmonisation work began in more systematic manner. Thirdly, after introduction of anti-retroviral (ARVs) monographs for the first time in world, the other pharmacopoeia bodies realised the value of IP, its approach and started coming forward for monographs harmonisation (from IP to their pharmacopoeias). This took time. Though sub-committees of IPC may be working with time bound targets and good deliverables, a few of the groups may not be sticking to timelines and I feel that may be lagging time. You know that IP is a social document and its contents (the standards) need not be unnecessarily cost escalating. This thinking also might play an important role in harmonisation process.”
Strengths and shortfalls
However, there are a few shortfalls in the current edition of IP which remain neglected. Unless they are addressed, the harmonisation process will not achieve desired success. Bhargava informs, “The ‘General Notices’ chapter is to be looked into more carefully. Since requirements of general notices do not directly affect any monographs and release, these are not properly worded.”
He draws attention to IP’s general notices page 11, second column, para 1, which states, “An article is not of pharmacopoeial quality unless it complies with all the requirements stated in the monograph. This does not imply that performance of all the tests in a monograph is necessarily a prerequisite for a manufacturer in assessing compliance with Pharmacopoeia before release of a product.” He points out that a general understanding of this sentence is that all the tests mentioned in the monograph need to be performed, however even before completion of all the tests the product can be released.
He further explains, “In the above example, I have a feeling that even if the above sentence is not mentioned in IP, nothing substantial will affect the quality of IP products. There are several such examples that can be cited. For instance, manufacturing technology of APIs has improved and the whiteness of IP materials has improved substantially, but IP continues to have description ‘off white powder’ and the junior chemist is compelled to mention a very white powder as off white. You will agree that IP is used equally both by junior analysts who are at the beginning of their careers and senior ones and IP should correct such anomalies. I remotely have a feeling that IPC’s officials ‘justify’ more than correct even though the corrections are minor,” says Bhargava.
However, according to Nayak, the current edition of IP has many positives as well. He explains, “There are no shortfalls in IP. It has covered a lot of ground. In fact, now we are trying to make our own monographs. So, developments are positive. Even countries like Sri Lanka and Myanmar are using our pharmacopoeia.”
A continuous process
Harmonisation is expected to be a continuous process but for late starters like IP it will be a big challenge. IP is still in the process of filling the backlogs.
As per USP spokesperson, harmonisation processes differ depending upon participation. He gives an example, “Pharmacopoeial Discussion Group (PDG) has a formal process that is publicly available and a timeline for individual standards. Harmonisation is achieved when all pharmacopoeias have highlighted harmonisation and any residual differences, based on a general policy in the national or regional area.”
Industry experts feel that though currently India has a lot of ground to cover, as far as harmonisation is concerned. They also recommend a system by which harmonisation will remain a continuous process. They caution that a laid-back attitude in this regard will continue to hamper the reputation of Indian pharma companies in the international market.
Bhargava informs, “Though IP publishes draft monographs for public opinion and also corrections, I am not too sure if there an IP newsletter for technical inputs, publishing its approach for harmonisation. Since there is a world pharmacopoeia forum and IPC’s Scientific Director is an active member, progress towards harmonisation and possible outcome may be made available to public through such newsletters.”
A win-win situation
Though the Indian pharma sector is globally known for its generic prowess, unfortunately, there have been cases when it has been criticised for its below par product quality. Harmonisation of IP will surely change this scenario. It is a major step towards making export oriented pharma players improve their standards.
Uttam Jain, Director, Neon Laboratories, informs, “While exporting to overseas markets, Indian companies have to comply with USP/ BP/ EP standards. At the same time, they have to use raw materials of IP standards and manufacture products as per IP standards while supplying to the Indian market. This increases cost, time and energy. It will be saved after harmonisation.”
Once harmonisation of commonly used monograph is done then all the manufacturers have to just comply with the globally accepted standards. This will not only strengthen the image and standard of IP but also increase the country’s confidence levels in the international market.
Jain adds, “Harmonisation will make IP’s standards globally accepted and increase business opportunities for Indian manufacturers. We will have the capability to manufacture highest quality of drugs at affordable prices. So, harmonisation of pharmacopoeia will be very beneficial to all.”
USP spokesperson opines, “Generally speaking, harmonisation reduces manufacturers’ burden of having to perform analytical procedures in different ways, using different acceptance criteria, in order to satisfy pharmacopoeial requirements that vary across regions. And ultimately, harmonisation increases access to quality assured medicines to patients, especially in the context of generics.”
Though modern medicines have always remained central to the harmonisation debate, India has to look at the AYUSH sector. Ayurveda, a major component of AYUSH, has also faced quality related issues in the global market. A big chunk of the Indian population consumes ayurvedic medicines. However, for ayurvedic manufacturers, it is still a neglected sector as far as harmonisation is concerned. But, at the same time, they are also optimistic that the newly formed AYUSH Ministry will take necessary steps in this regard.
“IPC is responsible for editing/ revising/ updating/ publishing IP while Ayurvedic pharmacopoeia of India (API) is under responsibility of AYUSH. As per our knowledge, IP does not include ayurvedic monographs so far. IP contains monographs on 13 herbs (like Hingu, Brahmi, Shankhapushpi, Marich, etc.) however, those cannot be considered as ayurvedic monographs,” opines Shashank Sandu, Director, Sandu Pharma.
Bhargava signs off saying, “The biggest advantage of harmonisation for manufacturers will be uniformity of quality standards, no more different IP/ BP/ USP requirements. There will be standardised quality, all countries will follow the same standards. Formulations of medicines for public will be a much simpler exercise, ultimately benefitting the patients.”