Biocon seeks withdrawal of application for two biosimilars under European drug regulator review

Shares of Biocon fell 6.26 percent and were trading at Rs 327.55 on BSE in early trade after the company said it sought withdrawal of dossiers currently under review for marketing authorisation by Europe drug regulator for its biosimilars of cancer drugs Trastuzumab and Pegfilgrastim.

“The European regulatory authorities had informed us of the need for a re-inspection of our drug product facility for these products,” Biocon said in a disclosure to stock exchanges.

“The request for withdrawal of the dossiers and re-submission is part of EMA (European Medicines Agency) procedural requirements linked to this re-inspection and will be considered by the EMA’s Committee for Medicinal Products of Human Use (CHMP),” the company added.

Biocon said it is on track to complete its 'corrective and preventive actions' (CAPAs) by the end of this quarter and intends to seek re-inspection and re-submission thereafter.

“This is part of a regulatory process,” Kiran Mazumdar-Shaw, Chairperson and Managing Director told CNBC-TV18. “These regulatory processes are extremely complex."

The French National Agency for Medicines and Health Products Safety, known as ANSM, inspected the Biocon's Bengaluru plant on behalf of the European Medicine Agency (EMA) between March 13 and March 17.

While the French drug regulator last month approved Biocon’s drug substance facility for Trastuzumab and Pegfilgrastim, it found lapses at Biocon's Bommasandra product facility in Bengaluru with respect to good manufacturing practices (GMP) for activities related to three biosimilar products.

EMA was reviewing Biocon's three biosimilar products — Fulphila (Pegfilgrastim), and Ogivri (Trastuzumab) for marketing authorisation in European Union.

The ANSM raised 35 deficiencies, including 11 major deficiencies, concerning biosimilar products.

Biocon is the first company to file for marketing approval of Trastuzumab in Europe. The re-inspection could potentially delay the arrival of first biosimilar Trastuzumab drug in Europe market.

Below is the verbatim transcript of the interview.

Surabhi: I understand that you have given the release to the exchanges. What prompted the withdrawal? What happens right now and what is the damage control that you are looking at from your end?

A: Please do not use such words because I really want to basically share with all of you that the regulatory processes involved for biosimilars and new biologics are extremely complex. I think the danger we have is to keep trying to compare it to simple Abbreviated New Drug Application (ANDA) and generics. So please understand that there is a regulatory process, there are administrative processes involved.

As you know, this is linked to a re-inspection intimation that we got from European Medicines Agency (EMA) for our drug products facility, if you remember and this is something that has been shared with you in the past. We have fought for a withdrawal of our dossier for re-submission based on this re-inspection. It is a part of a regulatory process. Now, this information we are sharing with you to tell you that we are on track, as we have shared with you, to complete our kappas by the end of this quarter. We will then seek re-inspection and re-submit the dossier which is what we have indicated to you in our statement.

So please understand this is a part of a regulatory process. These regulatory processes are extremely complex. So do not please read anything into it and start speculating a lot of things because we have to go through a regulatory process. We have fought withdrawal and this is the information that is coming out.

Varinder: Is this voluntary or is this forced on Biocon in terms of EMA?

A: What do you mean by voluntary or forced? Please understand when it is part of a regulatory process, we have to go for it. Now for instance, you know that this re-inspection is not something that we anticipated. So as a part of the re-inspection, we have to seek this withdrawal. This is all part of it.

Varinder: And how much time will it take?

A: This is all dependent on when we will be re-inspected. We are going to seek re-inspection in Q3 and as soon as we are re-inspected, we will give you the timelines of when we expect the approval.

Varinder: Will this have any impact on the US Food and Drug Administration (FDA), that most critical day which everyone is watching out.

A: Please understand that US FDA and EMA have no connection. US FDA goes according to its own regulatory track, EMA goes according to its own regulatory track. We have clarified this in the past. Please understand that this has no connection with anything to do with US FDA. This is connected with the re-inspection request or notice, should you say, from EMA, for our drug products facility. I would like to reiterate that we got an approval for our drug substance facility, but we got a request or a notice of re-inspection for our drug products facility. As a part of that, we have to basically withdraw our dossier and resubmit the dossier and we are ready to seek re-inspection in Q3, as we have discussed in the past. And we have already stated this position in the past. So we are on track as per what we have stated.

Vikas: A quick clarification. Since there are a number of observations that have been put forth by the French regulator, what do you think will be the timeline for addressing those, out of which 35, 11 were said to be serious.

A: Please understand, we have already said to you that we are on track to complete these kappas by the end of this quarter which means that we are on track and we are confident of completing these kappas by the end of this quarter and I said to you just now that we will be seeking re-inspection in Q3. So as soon as these quarters are completed, we will immediately seek re-inspection from EMA. Now, it is beyond my control to know exactly when they will come for that re-inspection. Will they come immediately, will they come in two months, will they come in one month? We do not have optics on that. So it is our hope and desire that they will come and inspect us at the earliest. But we have no way of understanding when they will come.

Vikas: You also explained that the US FDA process of examination is separate from what the EMA is doing, but at the same time, we also hear announcements from both the regulators that there is a constant exchange of information. In that light, do you think there will be some kind of an evaluation that the US FDA may also do of what the European Union (EU) is finding?

A: Please let me tell you that there are obviously regulatory sharing of information in terms of the inspections. I agree with that. Obviously we know that some of these inspections will be made aware and we ourselves are made US FDA aware of this inspection report that we got from US FDA. So it is not as if to say we are not sharing it. We ourselves are voluntarily sharing these kind of reports that we get from EMA and so on and so forth.

Now the point is please let me tell you, the review process is a very separate process. EMA and US FDA will do their own review processes. Please let me tell you that as far as the review processes are concerned, each one will evaluate. As you know, you have gone through and Oncologic Drugs Advisory Committee (ODAC) with US FDA where they have actually reviewed everything about our product. What they will be looking at is definitely the good manufacturing practice (GMP) status of these plants.

So again I just want to tell you that please do not confuse GMP and the dossier review of the other aspects of the product. So what happens is there is a clinical evaluation, there is a chemistry, manufacturing, and controls (CMC) evaluation and then there is a GMP evaluation. Each one of these has different tracks at both agencies. And what we are talking about right now is a current good manufacturing practice (CGMP) track where we have had this unfortunate re-inspection request by EMA which we are working towards and we are on track to complete the kappas by the end of the this quarter and we are going to seek re-inspection at the earliest.

Vikas: A quick one on the evaluation process that might happen for some of the other filers which had also filed around the time when Biocon had also filed. Do you think because this review process has been delayed, there may be a chance that even those other filers may also see an extension of their inspection process because so far, we do not know if their inspections have happened?

A: No, I cannot comment on that. I cannot be speculating on what is happening with others. I can only share with you what is happening to us and I am going to focus on this. I do not want to get distracted with all these other scenarios. I want to focus and make sure we get approval at the earliest. It has been a very disappointing setback for us, as I have already said to you, but we will make all attempts to get back on track. I want this approval at the earliest. Now we are going to try. We are making all efforts and this is part of that process. So I just want to share with you, please do not start speculating randomly and start imagining the worst. Please do not do that. This is a regulatory process which we have to go through and biosimilars review and approval process is extremely complex. Please let me explain that also to you.

Surabhi: Can you just help us understand how to look at the numbers afresh, in light of the present circumstances? Some of the reports that I am looking at are giving the EU market a size of about 2 billion, the US market a size of about 2.5 billion for this drug. So obviously we have to shift estimates by a couple of quarters now. You said Q3, you are hoping to hear from the EMA, so what should we pencil in in terms of revenues by next year maybe?

A: Please understand, you know that the launch of these products were never going to happen this fiscal. It was probably going to happen, at the earliest, late next fiscal. We are hoping that the material impact is minimal. I will only be able to give you more optics on this as soon as we are inspected.

Surabhi: Could the first two filed status be under a bit of a cloud with the EU market given that the timelines are now shifting?

A: I do not believe so, but I do not want to comment on it till I know what is happening with others. If anyone files, you know that it takes a certain amount of time to review.

Varinder: So according to you, at least for analysts, for September 3, there should be no connection, nothing changes in terms of the September 3 date which is in front of the company?

A: Please, I do not want you to confuse EMA with US FDA. I do not want to comment on such things. I want to focus on EMA right now. I do not want you to confuse the two things because you are linking the two things which is very wrong.

Varinder: Were you surprised by all the re-inspection and there are a lot of things which has happened with Biocon in the last 2-3 months because we have never heard anything.

A: Yes, I was. Absolutely, but this is the India effect. Unfortunately, we have to face it.

Varinder: You said that you are really disappointed by what has happened in the last 2-3 months.

A: Yes. I am disappointed because this is the first time we have had these kind of, this is the first time we have had a re-inspection request. This is not something that we had expected because we have had a very good track record of compliance and you know that this is a very disappointing setback for us. But we are going to now go ahead and solve it because that is what we have to do now. I do not want to get into what if, what not, all this is behind us. I have to now focus on course correction and making sure that we get the things back on track and make sure that we are only focused on the regulatory approvals.

Prashant: You said India effect. Could you explain that?

A: Basically, India does not enjoy a very high quality credibility amongst regulators. You know that. And all the companies are impacted. You know the best of companies are impacted because of this particular scrutiny and you know that the way these inspections are being carried on are extremely stringent and extremely forensic in nature which never used to happen in the past. And therefore, when you look at the kind of observations that are being noted, I just believe that we need to be much more focused on ensuring that we do not get such observations in the future.

Varinder: That is very true, coming from Biocon which has a very neat past in terms of no observations or nothing at all.

A: Yes, this is the first time we have had this kind of observation and I am personally overseeing all these issues because I never expected this.

Varinder: Only focusing on EMA, even if the re-inspection happens in Q3, do you expect at least by the next one year from where we are sitting right now, the approval should come in?

A: That is the expectation and that is why I said that it will all depend on when does this re-inspection happen. I am hoping that it will happen sooner than later.