USFDA observations on Biocon's Bengaluru facility purely procedural

Moneycontrol News

The seven Form 483 observations made by the USFDA on Biocon's sterile drug manufacturing facility in Bengaluru earlier this month were related to cleaning procedures, according to analysts. It may not be serious enough to cause a delay of the much-anticipated approval of biosimilar Pegfilgrastim in US market, they believe.

The pre-approval inspection (PAI) was triggered after Biocon filed biologic license application (BLA) for a biosimilar version of pegfilgrastim in the US.

US FDA inspected the facility between April 23 and May 1 and issued seven Form 483 observations.

US FDA inspectors issue their observations on deviations related to cGMP or current good manufacturing practices at the end of the inspection on Form 483.

Pegfilgrastim is a biosimilar version of Amgen’s Neulasta used to stimulate the level of neutrophils, a type of white blood cell that gets damaged in cancer patients undergoing chemotherapy.

The drug has sales of $3.9 billion in the US.

The BLA of Biocon along with its partner Mylan for Pegfilgrastim was accepted in the US in February 2017.

USFDA issued a Complete Response Letter (CRL) seeking update of the BLA with certain Chemistry, Manufacturing and Controls (CMC) data from facility re-qualification activities post recent plant modifications.

The CRL did not raise any questions on biosimilarity, pharmacokinetic/pharmacodynamic data, clinical data or immunogenicity.

Biocon said it has responded to the CRL.

Biocon’s target action day (TAD) for Pegfilgrastim in the US is on June 4, 2018. Target action day refers to the day on which USFDA will announce its decision.

The seven observations made public by US FDA are
Observation 1: (i) It was not confirmed the disinfectants used in manufacturing areas cause log reduction in contaminants; (ii) to clean ceilings Biocon is using mops – should use spray
Observation 2: Some secondary areas don't have microbial monitoring when they should
Observation 3: The cleaning area surfaces were not cleaned well enough.
Observation 4: They need to change gloves more often; shouldn't use the same wipe on two different surfaces
Observation 5: Biocon needs to use better-controlled filling speed for flasks

Observation 6: The warehouse temperature deviated a few times Observation 7: Check flasks after cleaning them; check the lids; wait for the green light

“We view this 483 as being on the lighter side and reasonably addressed through a change in procedure, additional training or hiring my grandmother, who seems to be fixated on cleaning issues. We do not believe these observations will delay the tentative June approval of Biocon/ Mylan’s Neulasta. Further, we note Mylan/Biocon's description of the 483 letter as ‘part of continuous improvement’ is fair and contributes to the broader credibility of the company,” said analysts of Bernstein Research