Azad India: Corruption in FMD Vaccine Quality Control in National Disease Control Program and Silence of Drug Controller General of India

मुंह पका खुर पका रोग के वैक्सीन की गुणवत्ता में घोटाला और ड्रग कंट्रोलर जनरल ऑफ इंडिया (DCGI) की चुप्पी: ठगा जाता किसान और भारत देश

#Corruption in #NADCP #India

Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals. The disease was initially described in the 16th century and was the first animal pathogen identified as a virus. FMD is a vaccine-preventable disease and several countries are free of FMD. As per WTO guidelines, countries free from FMD do not import animals and their products from countries having the disease. Due to the restrictions on exports of animal products from India to all the FMD free Nations Indian livestock owners lost about Rs. 20000 Crores every year. Besides, the government of India spends Rs. more than 2500 Crores every year for the control of the disease in India (https://pib.gov.in/PressReleaseIframePage.aspx?PRID=1598062#:~:text=13%2C343.00%20crore%20for%20five%20years,the%20economic%20output%20of%20farmers.) under Mission Doubling farmer’s income by Govt. of India.

The control of any disease through vaccination is dependent on several factors such as timely vaccination coverage, vaccine potency to induce herd immunity, and vaccine quality. The vaccine quality is of prime importance because if the quality is compromised all other efforts are wasted. To ensure vaccine quality Indian Pharmacopeia (IP) rules are implemented by the Drug Controller General of India and DCGI staff. However, to keep FMD live forever DCGI and its associates have flaunted the guidelines of the IP and OIE-World Organisation for Animal Health (https://www.oie.int/eng/A_FMD2012/docs/2.01.05_FMD.pdf).

To control FMD multivalent inactivated whole-virus (strain O, A, and Asia one of FMD virus) a preparation is formulated with adjuvant prior to use in the field. The introduction of this killed FMD vaccine has been extremely successful in controlling and eradicating the disease in many parts of the world where the disease was enzootic. As per OIE guidelines, the finished vaccine must be shown to be free from a residual live virus. This is most effectively done using in-vitro tests on concentrated inactivated virus preparations prior to the formulation of the vaccine and freedom from the live virus is subsequently confirmed during in-vivo and/or in-vitro tests on the finished product. The presence of the live virus is detected through NSP (non-structural proteins, only expressed in the host when a vaccine contains the live virus) antibody test done through in-vivo tests.

However, the Minutes and proceedings of the second National Steering Committee (NSC) meeting for the National Animal Disease Control Programme for FMD and Brucellosis held on 20th November 2019 clarify (on pages 9-11) that if an FMD vaccine fails in the NSP test (the test is done for the purity of the vaccine and assures that all viruses are killed in the vaccine, as this test is positive only when antibodies for nonstructural proteins are detected after vaccination;), only 40% of the Balance payment amount (25%), i.e. 10% of the total payment will be given to the manufacturer. The remaining 15% will be the penalty imposed on the manufacturer. The NSPs are expressed in an animal only when there is an FMD virus infection; which means the vaccine is capable of causing infection of FMD. The expression of NSP indicates that the vaccine is of sub-standard quality and capable of spreading the disease and causing disease outbreaks. In the past several post-vaccination outbreaks have been reported from different parts of India including in the Premier Indian Veterinary Research Institute, Izatnagar. Releasing 85% of the payment (vaccine cost) to the producers of such vaccines is treachery to the Nation, instead, such pharmaceuticals producing the vaccines capable of spreading the disease must be harshly punished and blacklisted forever. Instead, the members of the National Steering Committee meeting for the National Animal Disease Control Programme decided to reward pharmaceuticals for producing the vaccines capable of spreading the disease by advising the Government for the release of payment.

Such firms would have been blacklisted and penalties to the tune of many times the total amount of vaccine should have been imposed. Further, who will compensate the livestock owners and who will inform them of their animals being administered poor quality vaccines. Further the vaccine is also administered to cattle and it is not known how many cattle have faced adverse health effects or have died and if died. Using a vaccine not protecting the cows but has the potential to cause the disease is an intentional cow slaughter and a heavy punishment is prescribed for cattle slaughter.

As per the NSC meeting minutes, the vaccines inducing SN50 antibody titers (1:64 for Serotype O and 1:48 for Serotype A and Asia-1) in 75% (12 out of 16) animals of each of the potency testing groups will satisfy the criteria for acceptance of the vaccine quality. There is no available literature reference in the Indian Pharmacopoeia and OIE manual for using the proclaimed antibody titer-based criteria and seems to be an arbitrary assumption by the biased (towards Vaccine producers).

As per OIE, the finished vaccine must be shown to be free of residual live virus. This is usually done by combining in-vitro tests on the inactivated virus preparation and in vivo tests with the finished vaccine. Challenge tests are also conducted in vaccinated cattle to establish a PD50 value, although a serum neutralization test is considered satisfactory where the vaccine producer has established a statistically significant correlation between protection and specific serum neutralizing antibody ( https://www.oie.int/doc/ged/D7722.PDF). However, the biased NSC has not mentioned it as a required test. Why? No one knows.

As per OIE, (https://www.oie.int/eng/A_FMD2012/docs/2.01.05_FMD.pdf) the shelf life of conventional FMD vaccines is usually 1–2 years at 4°C (maximum range 2–8°C), but they are temperature labile and should never be frozen or stored above a target temperature of 4°C. The stability of all vaccines, but particularly oil emulsion vaccines, should be demonstrated as part of the shelf-life determination studies for authorization. However, the biased NSC again maintained silence over this aspect and did not mention it as a required test. Why? No one knows.

The FMD vaccine used in India is an oil emulsion vaccine for which stability of the emulsion is recommended for all emulsions by the IP. It is mentioned in all old volumes of IP (IP 2014, on page 955 of volume 2) mentions that “Injections that are emulsions should not show any evidence of separation-------”. However, the NSC flaunted this requirement of IP in their guidelines for monitoring the FMD vaccine used in NADCP.

The NSC recommended that “ten vials of every batch of FMD vaccine produced by the manufacturers will be collected on a random basis out of the whole lot of each batch by the officials authorized by DAHD/NAFED. Vaccine manufacturers will facilitate such collection of vaccine samples and the maintenance of the cold chains for transportation. Samples of all the batches collected by the officer will be submitted to the designated institute”. However, the IP (2014, 2018) (page 59 of chapter 2.2.11.STERILITY of IP 2014) (https://www.pharmaguideline.com/2011/11/sop-for-procedure-for-sterility-testing.html) and European Pharmacopoeia 2008, recommended that for sterility testing of FMD vaccine, 20 vials should be used. Why did the biased NSC reduce the number of vials of each batch to be tested to 10 only the members can understand?

The reality is still more bizarre, instead of 20 vials, the NSC recommended 10 vials and the testing agency received only 7 vials of each batch i.e., the implementation of biased guidelines of the NSC was further diluted.

The NSP guidelines were flaunted by not taking any action against defaulter vaccine producers. The Guideline mentions that “ If three consecutive batches of vaccines of a particular manufacturer fail QC tests, then purchaser/ Nafed shall not take supply from the vaccine manufacturer concerned and this information shall be shared with the Department (DADH) so that DCGI is informed for taking necessary further action.” Though the department informed DCGI to take action against defaulter firms (as 9 batches of three firms failed consecutively) but DCGI has not initiated any action indicating a coalition of DCGI and producers of substandard FMD vaccines to bluff the country for the program costing Rs. 13343 Crores.

The NSP guidelines (page 7) mention that “The sample vials will be coded and anyone out of every 5 batches will be randomly selected and will be sent to three laboratories designated by DAHD for testing of the FMD vaccine. 16 cattle for potency, 2 cattle for safety and 2 cattle as control of 6 to 8 months of age will be used for quality control testing by these laboratories.” In the year 2020, a total of 169 batches of FMD vaccine for use in NADCP were used and sampled and as per rule 32 batches must have been tested but no more than 25 batches have been tested and who knows that they were either randomly chosen or targeted ones. Of the ten FMD vaccine batches sent for testing to one of the institutes 9 failed while one passed was also in a real sense must have failed as NSP antibodies were detected in inoculated animals but passed. This means that the majority of the vaccines of FMD used were of substandard quality.

Besides DADF other people have written to DCGI long ago. Still, it has not taken any cognizance of the ongoing corruption in FMD vaccine quality control probably due to its own involvement. As a result of the use of substandard FMD vaccine FMD outbreaks are occurring in many places and farmers (livestock owners) are suffering due to rampant corruption in the system. The whole episode mentioned above indicated that a corruption syndicate is working at a very high level in the country and an urgent intervention is needed in the management of NADCP and its funds.