EU Falsified Medicines Directive Industry proposes, Regulator disposes?

As the deadline for the implementation of the EU’s Falsified Medicines Directive draws near, exporters of APIs to the EU and the Drug Controller General (India) have been locked in discussions trying to find ways to meet the Directive’s requirements, without delays. Usha Sharma presents some perspectives from API exporters and industry associations

‘Entire re-process leads to delay in export consignment’

N R Munjal

The European Union has recently notified Switzerland as a country which is equivalent in the implementation of GMP requirements to that of EU GMP. The requests of other countries like Brazil, Israel, Australia and Singapore are under examination by EU for equivalence assessment. Our industry is also of the view that, inspecting/Indian GMP being followed/ enforced for APIs under the provisions of Schedule M of Drugs & Cosmetics Act is also equivalent to EU CGMP. We strongly feel that hassles of issuing written confirmations (certificates) to each company exporting the APIs can be avoided, if DCGI takes up the matter with European Union towards accepting Indian GMP as equivalent to EU CGMP. Then there will be no need to be inspected again.

For all practical purpose, WHO GMP inspection takes approximately six months from the application to receipt of certificate. And cost is negligible and not the criteria. The entire re-process leads to delay in export consignment, if the time bound procedure is not implemented, it will for sure result in delays of export consignments.

To issue certificate to all licensed API exporters for their use with each exported consignment.

In case India cannot get listed on the EU’s list of countries, DCGI may give a certificate to all the licensed units in India confirming that our units confirm to the following:

1. The standards of Good Manufacturing Practice (GMP) applicable to the plant manufacturing the exported active substance are at least equivalent to those laid down by the Union pursuant to the third paragraph of Article 47;
2. The manufacturing plant concerned is subject to regular, strict and transparent controls and to the effective enforcement of good manufacturing practice, including repeated and unannounced inspections, so as to ensure a protection of public health at least equivalent to that in the Union; and
3. In the event of findings relating to non-compliance, information on such findings is supplied by the exporting third country to the union without any delay.

A certificate of the above nature can be used by the manufacturing units in India exporting APIs to the European Union by enclosing a copy of such certificate with each of the consignment, which could be acceptable to the EU Authorities.

There should be a time bound inspection certification programme initiated after a consultative committee comprising of DCGI representative, pharmaceutical associations representatives and Ministry of Commerce representative to take the decision regarding the time frame and procedure to be followed.

– N R Munjal, Vice Chairman cum Managing Director, Ind Swift Laboratories

‘The DCGI can delegate the certification process to local FDA’

Aditi Kare Panandikar

The approval of COPP is being granted, with a validity of two years, based on facility inspection by WHO authorities. Also, the manufacturer shall be committed and abide by the Schedule M regulations for GMP compliance. So repeat inspection is not necessary. The inspection can be considered, if any new API is intended for export to Europe, which is not covered in the list of granted COPPs. Also for firms not having COPP, inspections may apply. The DCGI shall rely on their own grant of COPP and shall consider other regulatory approvals like US FDA, TGA etc. The DCGI can also utilise this as a tool for improvising the confidence of European countries on Indian manufacturers. The written certification shall be a one time grant having a reasonable validity of two years. This certification shall be product wise and need not be applied to every batch or consignment.

The current COPP approval or renewal process takes approximately six months, including inspections. It is subjected to nature of observations and relevant compliance. As the EU Directive 2011/62/EU is a new initiative, the DCGI has not arrived at any specific time lines. However, the DCGI has to speed up the process as the effective date of EU directive is approaching fast. As the inspections are not felt necessary to initiate this process, specific timelines may not be applicable. The cost involvement may be only the respective fees, if any assigned by the DCGI.

If the DCGI decides to inspect the facility prior to giving the written certificate, then it will definitely cause delay. Considering the number of API manufacturers and exporters across India, DCGI may find it practically difficult for inspections within the set timeline.

The DCGI can delegate the certification process to local FDA. One more reason for this delegation is every DCGI inspection is a joint inspection of DCGI and local FDA. The local FDA has periodic and more frequent checks on the companies. This can minimise the load on DCGI.

The local FDA is more approachable for companies in suburban industrial areas. This will also be beneficial to the companies whenever a new API is identified for European export. Hence, the certification process will move fast and boost the export business of the companies.

There should be a particular time frame for approval. Timely approval facilitates the export of APIs in a timely manner and leads towards customer satisfaction. Also this will benefit the companies to continue the business in Europe and minimise the competition from other countries.

Obviously the approval process shall be completed before 02/07/2013, as the EU directive has given enough lead time.

– Aditi Kare Panandikar, Managing Director, Indoco Remedies

‘There is not enough time and manpower’

Daara B Patel

Any facility that has any of the international approvals such as WHO GMP or US FDA, EDQM, UK MHRA, etc. need not be inspected again as these units are being inspected regularly. Whatever time it takes to inspect one unit, there is not enough time and manpower to implement procedures of inspection of all API units in India who exports to EU countries, not to mention the huge documentation that would be required.

If the CDSCO goes by the letter of the rule and not the spirit behind it, it will delay almost all consignments, as the inspections will need to be completed now, since the companies take up manufacturing activities for fulfilling orders two to three months in advance.

We have requested the DCG(I) to consider an automatic route for units holding WHO-GMP or any of the universally recognised international regulatory approvals as mentioned earlier. The DCG(I) could, for example, certify that the unit meets with the requirements of EU standards, based on the most recent inspection by any of these regulatory authority as above.

If DCG(I) decides to follow the automatic route, then the whole process is eased to a large extent as certification should not take too much time. Almost all the manufacturers without exception exporting to EU would have WHO-GMP and any of the other international approvals. Our government has to ensure that exports of APIs to EU do not suffer and continue without delay.

– Daara B Patel, Secretary, Indian Drug Manufacturers Association (IDMA)

‘It is a waste of time for regulators as well as for manufacturers’

B R Sikri

Once a manufacturer wants to start export projects, his first and foremost duty is to have GMP compliance as per WHO guidelines. Prior to this compliance, the company or manufacturer has to have Schedule M compliance. By the above two methods his unit is validated and qualified by auditors of Government i.e. Central Drugs Standard Control Organization (CDSCO) and State licensing authorities. The products being manufactured, whether for domestic need or for export, have to be a quality product as per rules and regulations under Drugs and Cosmetic Act.

Once the above exercise is done by the Government regulators, why should they accept the recommendations of EU draft guidelines? It is not only a duplication of the work done earlier, rather it is a waste of time for regulators and manufacturers. This will lead to delay of the consignment and people will get discouraged to export to various countries. Today, India is a proud country since we are the largest exporters of pharma products as we are third in volume, 10 per cent of global share and 14th largest by value. The day is not far off when India will be the second largest bulk drug manufacturer world wide by overtaking Italy. But if these hindrances are created by the Government or by outside agencies, it will certainly have a negative impact on the growing pharma industry.

India is losing its competitive advantage, becoming dependent on China. Almost every Indian DMF is filed considering the Chinese intermediate supplier as alternate source. If duplication of work starts taking place by inspecting the Indian units, China will become more aggressive and will try to take undue advantage of the situation. China is already working on macro strategy with the result that slowly and gradually intemediate industry is moving out of India. Satran, prazols, microlytes are classic examples of intermediate sourcing.

Taking Schedule M compliance clearance, taking WHO GMP certificate itself is a big exercise because it is quite an expensive exercise and by adding another audit or inspection by DCGI, this will add fuel to the fire.

While granting the WHO GMP certificate, the requirement of EU guidelines can be strictly adhered too instead of duplication. Instead of wasting time, Government should come forward to build infrastructure in the areas of innovation, sophisticated testing labs. There is a need for promoting incubation centres to realise the ideas with first generation entrepreneurs.

We appreciate that nowadays a specific time frame is being followed by CDSCO in inspecting the units for WHO GMP certification and delays are being avoided, but adding this duplication of inspection will be a futile exercise on the part of the Government, particularly when they have limited manpower and in many other areas due to which there is a delay in clearing industry applications. The impact of such duplication will be more painful to SMEs as the small players continue to run out of steam in the battle for survival while big players are growing from strength to strength. Therefore, it is high time the Government avoids such an exercise because it is the same CDSCO who wants to inspect our facility, emphasising on quality parameters and will provide approval for a particular batch or consignment and the same officer/ auditors/ inspectors, would have audited the plant at the time of GMP certification.

– B R Sikri, Co-Chairman FOPE, Vice Chairman, CIPI, Vice President, BDMA, Secretary, IDMA Board of Himachal and Uttarakhand

‘Directive will promote more of EU industries’

Bhavin Mehta

I feel if the facility has WHO approval then it need not be visited since regulations specified by WHO are similar to the EU regulation but DCGI is the competent authority and it shall decide what is best in the interest of the EU directive.

The inspection shall take one to five days depending on the size of the plant and number of the molecules are involved for the export consignments.

I believe that Pharmexcil has taken very proactive steps in order to ensure this does not happen and Dr PV Appaji, Director General, Pharmexcil has requested DCGI, and DCGI has also assured to look into the matter and it is conveyed that there are no delays in clearance of export consignments. Since, Ministry of Health (MOH) has officially deputed DCGI and EU directive also specifies for competent authority, we need to follow the guideline.

In order to promote API sourcing within EU, this directive will promote more of EU industries than outsourcing to be done from world over and hence Pharmexcil is keen to ensure India implements the same and exports are not affected.

Pharmexcil along with DCGI is working on the same, since export orders are based on letter of credit (LC) vendors will have to ensure that this is done before their expiry. Usually vendors get LC’s in the range of 30-90 days and it needs to be taken care of within this period.

– Bhavin Mehta, Director, Kilitch Drugs

‘DCGI needs to provide clarity on how it will proceed and timelines’

Pranesh Raj Mathur

We do not believe that pharmaceutical manufacturing facilities need to be inspected again. It may not be relevant for authorities to re-inspect a facility if the unit has already had some other inspections carried out such as WHO, GMP or COPP. The DCGI could specify some standard that all facilities need to adhere to and exempt all the facilities that have these approvals from further inspections.

Particularly about time and cost involvement, the entire inspection process mainly depends upon the modality with which the DCGI wants to carry out the inspections. If they are trying to do this from their central office in New Delhi, then it is going to be a very laborious process. I do not think that the DCGI Delhi has the administrative wherewithal to carry out all the inspections for all the plants located in the country. Even if they delegate this task to local bodies, it is going to be quite a task for the local authorities to carry out so many inspections especially in a state like AP where there is a big concentration of pharmaceutical companies; it will be an extremely difficult task for local authorities to complete all the inspections on time.

It will definitely delay export consignments if the inspections are not completed by the deadline. If Indian companies aren’t ready in by the deadline, it will have an adverse impact on how European customers view us a reliable source and will hurt our industry and employees.

An alternative could be to allow all the companies that have approvals – international or local – to export without inspection. This would make it faster and cheaper. A lot of pharmaceutical companies in India have approvals like US FDA, EDQM and local government approvals, not to mention DGCI approvals and these companies also have compliance with GMP processes. The DCGI can set up standards like this and take a decision that exempts all companies that have these approvals from inspection.

All the shipments sent to EU regions after July 1, will require this certification. If we consider a sea shipment of at least 30 days, they will need to give this approval before the end of May. Failing this, consignments will get held up and delayed. The DCGI needs to provide clarity on how it will proceed and timelines for those steps so we can communicate it with our customers.

– Pranesh Raj Mathur, President – API, Granules India