Suspension of 700 Marketing Authorizations in EU may cost India $1.5 billion worth pharma exports by March 2016

1. GVK BioSciences:
Blunder or Blown out of Proportion?
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2. What is ?
• Part of GVK conglomerate
• Provides R&D, contract manufacturing, discovery research, clinical
development, formulations and informatics services to over 300
customers
• Based in Hyderabad. Centers in Mumbai, Bengaluru, Hyderabad,
Gurgaon, Ahmedabad and even in US (recently acquired)
• Certified Clinical Research Centers: Hyderabad and Ahmedabad
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3. •GVKBIO stands above its competitors when it comes to regulatory
approval process, turn-around-time and reporting quality. The
facilities are audited by DCGI, US FDA, ANSM, WHO, MHRA, ANVISA &
MoH Turkey, thereby crediting it with global submission footprint
•GVK BIO provides a complete spectrum of Clinical Research Services
right from Phase I to III clinical trials which includes, Clinical
Operations Services, Project Management Services, Clinical
Monitoring Services and Medical Monitoring and Advisory Services to
Late Phase Clinical trials
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4. What happened?
• Inspection of Hyderabad facility by French Authorities ANSM (Agency for
Medicines & Health Products Safety) in September last year
• Raised concerns over GCP guidelines followed during 2008-14 period
• The concern: Systematic falsification of check-out ECG records as part of
bioavailability/bioequivalence (BA/BE) studies stretching over the last six
years (9 trials).
• Result: ANSM recommended suspension of marketing authorizations of all
MAHs having clinical trial data generated at GVK Bioscience, Hyderabad
facility.
Also, at the request of EC, EMA opened investigations, looked into 1000
products approved, ‘trialed’ at Hyderabad facility.
(700 MA suspended)
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5. Companies Impacted…
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6. Companies Impacted…
Sr. No. Therapeutic Area Molecule/Company
1 Anti-epileptic Donepezil (Mylan), Leviteracetam (DRL), Clonazepam (Sandoz)
2 Anti-diabetic Repaglinide (Mylan), Pioglitazone (DRL), Metformin (Actavis),
3 Anti-hypertensive/Anti-
hyperlipidemic
Candesartan (Mylan), Irbesartan (Torrent), Atorvastatin
(Mylan), Telmisartan, Valsartan (DRL), Amlodipine (FDC)
4 Anti-ulcerants Esomeprazole (Mylan), Pantoprazole (Lupin)
5 Anti-histamine Desloratidine (Teva, Zydus)
6 Anti-platelet Clopidogrel (Wockhardt)
7 Anti-depressant Escitaprolam (Abbott, Zydus), Venlafaxine (Alembic)
8 Anti-osteoporosis Alendronic acid (Ranbaxy)
9 Anti-infective Aciclovir (Ranbaxy)
10 Analgesic/Anti-inflammatory Ibuprofen (Zydus), Tramadol Paracetamol (Zydus),
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7. GVK’s Stand
• GVK officials maintained that the company had followed standard
compliance requirements throughout the stages of its BA/BE studies.
Additionally, it said it strengthened its operating procedures around
taking ECGs.
• Follows three levels of checks for every function starting from the
person who is assigned a task, which is reviewed by another staff
following which it is approved by another senior executive. The final
stamp of approval is given by the QA executive.
• In this case for check-in and check-out processes, GVK Bio said, the
same system is not followed as those were not part of a full-fledged
operation and varies according to the trial design and protocols
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8. • In their report to the company, ANSM is believed to have cast doubt on the
time taken to complete an ECG noting that the Indian CRO could not have
completed the ECGs on volunteers within a very short time.
• But GVK refuted the point and supplied videos of volunteers to prove that
each ECG can be completed in less than three minutes or five ECGs can be
done in a span of 10 minutes.
• Notably GVK Bio claims it has never encountered any critical findings in
about 20 audits that it has undergone in the last 11 years, since 2004.
• To add to the complexity, an official with GVK Bio said the U.S. FDA had
audited the same facility in August, three months after the ANSM audit,
but gave a clean chit to the facility on compliance standards
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GVK’s Stand

9. Was this the first?
• Two deaths in CT's acc. to a study in Indian Journal of Medical Ethics
1. Wyeth Pharmaceuticals – Pneumonia vaccine – St. John’s Hospital,
Bangalore
2. BE study of Felodipine – Hyderabad facility
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10. Was this the last?
Quest Life Sciences, Chennai
• Joint inspection by WHO & USFDA in October, 2014
• Issued five 483 and a NOC (Notice of Concern) dated 30th June, 2015
• Duplication of ECG reports and deviations from GLP & GCP observed
and cited in NOC
• Lifting only after submission of repeat study indicates BE was indeed
established
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11. Learnings from GVK case…
• Global regulators wont tolerate even a shadow of doubt when it comes to
safeguarding health of their citizens.
• Pharma companies from India will have to ensure that their protocols
measure up to global standards and scrutiny.
• Any shortcomings in requirements by EMA/US FDA results in suspension of
marketing authorizations which translates into huge loss of revenues for
the pharma companies involved
• Pharmaceutical companies must thoroughly review their contracted
organizations periodically for regulatory compliance apart from routine
regulatory body inspections
• Indian pharmaceutical and allied organizations need to let go of the
complacent attitude and adopt strict adherence towards international
protocol to attain trust of foreign regulatory bodies
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