Lupin's FDA Inspections, How Serious Are The Concerns?

Lupin’s FDA inspections, how serious are the concerns?

Lupin, India’s third largest pharmaceutical company by sales, was in the news recently as it recalled multiple batches of products manufactured at its facility in Mandideep (Madhya Pradesh, India).

The US Food and Drug Administration (FDA) announced the recall just one week after Lupin had announced a successful close-out of the FDA’s inspection concerns at its Mandideep facility.

In a statement to the stock exchange, the company had mentioned that the FDA had conducted audits at Lupin’s Mandideep facility from February 8 to 19 this year, and at its Aurangabad facility from January 11 to 15, 2016.

It isn’t all sunny in Goa

The statement made no mention of the status of FDA’s inspection at Lupin’s plant in Goa, the largest revenue contributor to Lupin’s US business.

In a recent interview, Lupin’s Managing Director, Nilesh Gupta, did highlight that while the inspections at Mandideep and Aurangabad were closed successfully, the company will “not get new approvals from Goa”.

The PharmaCompass team reached out to FDAZilla.com to gain access to the Form 483s issued by the FDA to Lupin’s Goa formulations manufacturing facilities, where Lupin had expanded capacities by 50 percent last year.

The manufacturing plant in Goa has been inspected twice by the FDA in the last year and a review of both inspections indicates a bumpy road ahead for Lupin.

“With Goa and Mandideep, almost entire US business for Lupin (ex-Gavis) has come under regulatory scrutiny,” says a Capitalmind report.

‘Testing into compliance’ instead of finding the root-cause

Simply put, in case there is a problem in the quality of a product, Good Manufacturing Practices (GMP) require that the company identifies the root-cause that triggered the problem.

“FDA prohibits sampling and testing with the goal of achieving a specific result or to overcome an unacceptable result (e.g., testing different samples until the desired passing result is obtained). This practice, also referred to as testing into compliance, is not consistent with cGMP (current GMP),” states FDA’s recently published guidance “Data Integrity and Compliance with cGMP”

In the July 2015 inspection at Goa, FDA investigators found seven instances where batches that generated ‘Out of Specification’ results and failed in-process specifications, had the finished product released by the quality control unit (QCU) and distributed without invalidating the out of specification results.

The investigators also found over 40 complaints, related to different batches of a suspension product which finally “the firm stopped manufacturing” but did not conduct an evaluation on in order to assess the need for any market action (for example, a recall).

Continuing with GMP malpractices

In March 2016, the FDA inspectors were back and once again they uncovered “no scientific basis for invalidating an initial out of specification” result.

The “testing into compliance” concern was further magnified as FDA inspectors felt Lupin “failed to design a process suitable for routine commercial manufacturing that can constantly deliver a drug product that meets its quality attributes”. The inspectors have cited multiple instances where “there is no high degree of assurance that the process is reproducible”.

In addition, FDA inspectors highlighted concerns over the cleaning procedures adopted at the Goa site. Instead of using a vacuum or dry wipe to remove the previous product, operators sprayed the product with water which resulted “in a large pool of water mixed with powder covering the floor of the production suite during the cleaning operation”.

Lack of management or quality assurance review of cleaning records, operators not following appropriate procedures to “prevent objectionable microorganisms in drug products” and cleaning procedures that were found deficient made the inspectors highlight the risk of cross-contamination between products at the facility.

Our view

Lupin’s recent recall of products from their Mandideep facility mentions “cGMP deviations: finished products manufactured using active pharmaceutical ingredients whose intermediates failed specifications” as the reason for the recall.

The concerns at the Goa facility are along similar lines. And it would not be surprising if Lupin starts recalling products made at the Goa facility.

In addition, while there are “no pending applications” for new drugs from Mandideep, Lupin’s new product filings from Goa could be impacted. Nilesh Gupta expects that within the next three months, Lupin should “close everything” it committed to the FDA.

However, given PharmaCompass’ experience gained from tracking problems at other major companies in India like Zydus Cadila, Mylan, Dr. Reddy’s, Sun Pharma, Ipca Laboratories and Emcure, we expect Lupin’s journey towards gaining favor with the FDA to be a lot longer.

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“ The article is based on the information available in public and which the author believes to be true. The author is not disseminating any information, which the author believes or knows, is confidential or in conflict with the privacy of any person. The views expressed or information supplied through this article is mere opinion and observation of the author. The author does not intend to defame, insult or, cause loss or damage to anyone, in any manner, through this article.”

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