Q. Your views on the outcome of the meeting held in February 2016 between the Indian pharma companies and the Regulators
I think this was a useful forum where various regulators from US, Europe and India could share thoughts with the pharmaceutical industry stakeholders in India regarding quality of product and GMP requirements. India is an important region that makes many critical drugs, so dialogue is good. I think we were successful hearing from stakeholders and in noting that our requirements are the same worldwide.
Q. Of late, Indian pharma companies are undergoing severe pressure because of the USFDA’s regulatory framework. Some of the Indian pharma manufacturers were issued warning letters pertaining to the manufacturing operations being carried out at their plants. Which are the areas you feel to be improvised and comply with your regulations?
The comment about “severe pressure” is confusing and potentially misleading. FDA inspectional frequency for the various regions, including India, is directly proportional to the number of firms producing drugs for the US market. There is no risk factor in inspectional decisions (where to go) that is based on geography – for any region. Indian firms are selected for inspection the same way, using the same factors, that a US firm or any other firm around the world is selected. Its important this be understood. Further, inspectional outcomes of US inspections of Indian firms follow similar trends of other regulator’s inspectional outcomes. The bottom line is Indian firms are selected and evaluated in a manner consistent with any other firm, in any other region.
Q. What are ‘Quality Standards’ specified by USFDA with regards to manufacturing?
FDA agreed this vision with industry stakeholders, academia, and other regulators some time ago:
“A maximally efficient, agile, flexible pharmaceutical manufacturing sector that reliably produces high quality drug products without extensive regulatory oversight.”
We view quality as a product fit for its intended use and free of contamination. This goal can not be achieved with end product testing alone and the GMPs as outline in 21 CFR part 211 are a critical pillar to that vision, as is a strong company quality culture and a commitment to operational excellence that begins at the product development stage with the use of QbD (Quality by Design) principles. Industry – including India – is working to achieve this vision and is making progress. At the conference I noted the draft and preliminary results of a sampling study which continues, but showed potential indication that India as a whole was performing at a similar level to other regions.
Q. What are the mandatory procedures Indian companies are expected to follow with regards to clearance of their manufactured products being marketed in the US?
Commitments made in applications, or requirements of various compendia such as the USP (in the case of the US market), along with the GMPs outlined in 21 CFR Part 211 are examples of mandatory requirements. GMP or ‘Good Manufacturing Practice’ are the regulations which provide a frameworks that supports product quality. GMP requirements are not definitive instructions on how to manufacture specific products; rather they forms a series of general principles and a legal framework that is designed to help prevent quality problems. But GMPs alone can not ensure quality any more than end product testing can and this is why FDA is driving towards a quality culture rather than simply a culture of compliance. There are many other important elements critical to producing quality products that are discussed in later questions. It may also be useful to note that there may be many ways to comply with GMP requirements and it is the company’s decision to determine the most effective and efficient way to do so. This provides flexibility, and allows the manufacturer to interpret the requirements in a manner which makes sense for each individual business operation.
The mandatory requirements are no different for Indian firms than any other manufacturer, are well known, and Indian companies are generally doing a good job. The Indian press tends to focus on those firms having issues, but India, like every other country or region, has some firms that are doing well and some firms that have failed an inspection and are in remediation to improve their processes. I want to stress that the whole idea of only looking at what is mandatory, or the focus on India alone, is misguided both in terms of US and Indian patient’s interests. It is well documented that the electronic and many other industries operate at a 6 sigma level. As noted by many third parties – including at the IPA conference – the pharmaceutical industry operates at a 2-3 sigma level. This is an industry problem, not an Indian problem, and because the costs of defects is so high in a 2-3 sigma process, the cost of life saving medicines is driven way up and the ability to reliably supply patients is driven way down as we have seen with the drug shortages. Indian and American – indeed ALL – patients deserve better. Why should their cell phone be produced to a higher standard than their life saving medicine?
Q. Quality assurance level differs from country to country as different countries have different resources and limitations. Under these circumstances, how does FDA imply the norms?
I must reject the premise of the question. Quality assurance levels do not differ from country to country if you look broadly at industry. If you understand that it costs many times more to produce a poor quality product via a 2-3 sigma process than it does to produce a high quality product via a 6 sigma process, why would you run a high cost – low quality process? Many firms around the world including India that used to run 2 lines – one for developed and regulated markets and one for the rest of the world – realized they were driving their costs up, not down, and now just run one high quality line. There is a fact that the question fails to understand: quality pays for itself many time over.