Total number of respondents: 78Number without endophthalmitis / 1 year: 661 endophthalmitis / uveitis / 1 year : 72 endophthalmitis / uveitis / 1 year : 13 endophthalmitis / uveitis / 1 year : 2>10endophthalmitis / uveitis / 1 year : 2Fractionation techniqueDirectly from the vial – 47Aliquots – 14Patient pooling – 8Direct and aliquots – 1From vial & pooled – 8Endophthalmitis / uveitis vs. technique of fractionationDirectly from the vial -5 practices 1, 1, 1, 2, 3(number reported from each practice)Pt pooling -3 practices 25, 1, 20Aliquots – 3 practices 2, 3, 1Dr.P.Mahesh Shanmugam, DO, FRCSEd, PhD, FAICO(VR)Head, Vitreoretinal & Ocular Oncology Services, Sankara Eye Hospitals, IndiaWhen Roche, the manufacturing company was contacted, this was the response we got:Dear Sir,
With reference to your query/complaint regarding Avastin usage in Eye and authenticity of vials. We understand that the enquiry is from an Eye Hospital and thus we became aware that you are using Avastin in ocular indications and it is our responsibility to make our position very clear.
We wish to inform you that Avastin is not approved for its use in any Ophthalmologic indication.
Please take note that under section 2.4 of Prescribing Information (attached) Warnings and Precautions
Severe Eye Infections Following Compounding for Unapproved Intravitreal Use (see section 2.6.2 Post Marketing)
Individual cases and clusters of serious ocular adverse events have been reported (including infectious endophthalmitis and other ocular inflammatory conditions) following unapproved intravitreal use of Avastin compounded from vials approved for intravenous administration in cancer patients. Some of these events have resulted in various degrees of visual loss, including permanent blindness.
Avastin is not formulated for intravitreal use.
Individual cases and clusters of serious ocular adverse events have been reported following unapproved intravitreal use of Avastin compounded from vials approved for intravenous administration in cancer patients. These events included infectious endophthalmitis, intraocular inflammation such as sterile endophthalmitis, uveitis and vitritis, retinal detachment, retinal pigment epithelial tear, intraocular pressure increased, intraocular haemorrhage such as vitreous haemorrhage or retinal haemorrhage and conjunctival haemorrhage. Some of these events have resulted in various degrees of visual loss, including permanent blindness.
We wish to make our position very clear as mentioned below –
Roche and Genentech are NOT developing Avastin for any ocular conditions
Avastin is investigated in cancer and approved for the treatment of metastatic colorectal cancer, advanced non-squamous non-small cell lung cancer, metastatic renal cell cancer, advanced epithelial Ovarian, fallopian tube and primary peritoneal cancer and for recurrent Glioblastoma multiforme and use of product in approved indication is recommended in updated country specific local prescribing information (attached copy of our local updated prescribing information
Avastin formulation has been developed for intravenous use only and should not be used through any other route of administration
Roche does not recommend the use of Avastin to treat any other conditions and cannot support the use of product through routes of administration different from that for which it was developed and registered.
Potential Concerns about Off-Label Use of Avastin in ocular conditions
· Patient safety is of utmost importance to us.
· Pre-clinical safety/toxicity – Since Avastin was designed for systemic use for the treatment of cancer and was not designed for the eye, no ocular safety testing has been done with AVASTIN.
· Sterility Aliquoting and storing Avastin improperly in syringes may result in contamination. The current Avastin formulation cannot be used as a multi-dose preparation because it does not contain preservatives and was not designed to be administered in this way. We are unable to recommend use of storage conditions or dilutions outside of those described in the Avastin updated local prescribing information and are unable to accept any responsibility for adoption of such alternative storage or use.
· Manufacturing – Avastin is not approved for ocular uses by either the FDA or the EMEA or even Indian Health authorities. Avastin’s formulation was designed for intravenous use for the treatment of cancer. Roche believes that an ophthalmic formulation would be required for use in any clinical trials of Avastin administered via the intravitreal route e.g. for the investigation of wet AMD, however, no such formulation has been developed by Roche to date.
We hope that this information helps you to be informed on Roche position very clear to you.
Further, our Drug Safety Team will get in touch with you to report this as an Adverse Event/Serious Adverse Event (if there are any) and our Product complaints would respond to you regarding the genuinity of the vial.
Dr Amit Qamra
Senior Medical Manager
Roche Products (I) Pvt. Ltd.,
1503, 15th Floor, The Capital,
Bandra Kurla Complex,
Bandra (E), Mumbai 400051
Tel +91 22 33941414
Fax +91 22 33941054
Cell No: +919819367795; e-mail email@example.com
Confidentiality Note: This message is intended only for the use of the named recipient(s) and may contain confidential and/or proprietary information. If you are not the intended recipient, please contact the sender and delete this message. Any unauthorized use of the information contained in this message is prohibited
Disclaimer: Roche Products (India) Pvt. Ltd. is providing this information as per our medical information process and to assist the doctors in making their own decisions about patient care. We do not recommend the use of our products for any indication, claim, dosage or route of administration not covered in the product’s prescribing information (PI). Articles that are attached with this mail are to be used only for academic purpose and should not be redistributed or used for commercial purposes
Adverse Event / Safety Reporting: In case you come across any adverse event with Roche medicinal product please report the adverse event at firstname.lastname@example.orgFinal observation:
Thank you for the mail. The situation is clear. Roche doesnt take any responsibility for the sterility issues arising out of off label ocular use in an unacceptable manner. We cant say anything against them.
The current panicky situation is out of lack of uniformity in use of the drug and also the greed among practitioners resulting in malpractice. Someone pools patients, someone keeps it in fridge n uses it as multidose vial, someone withdraws and stores in syringes, someone fractionates in pharmacy and uses aliquots, and many are there who share and carry in ice packs in the city or even in overnight journeys just to say that they have treated. Everyone has genuine explanation for what they do!!! In US and other places where this is used, fractionation in pharmacy maintaining asepsis is the accepted mode of use. They have formulated guidelines for fractionation and use after similar situation of serial endophs 2 years back. The pharmacies were blamed for the sepsis that time.
If a drug is safe for intravenous use(in terms of asepsis), it should be safe for any route of administration. There is no rule that if we used it offlabel for ocular use, they are not responsible for issues arising out of contamination of vial. They cant support their argument in this regard. If diclofenac got approval and intended for use in knee joint pain, it doesnt mean that we can not use it for shoulder joint pain. As a practitioner, we have the right to use our discretion in the interest of patient and use any medicine (even ayurvedic and homeopathic) for any patient. Only thing is, in case of a problem, we should have enough evidence regarding what we have done. We have enough evidence in literature for use of avastin in eye now. But the problem is with the way we practice. If someone opened a fresh vial and gave intraocular injection and saw endoph, and the culture of vial showed same organism as seen in the affected eye, its a genuine case against company. Is there such a genuine case in current scenario? If so, I request those who have evidence to take necessary action. If not, beating in the bush doesnt help much.
Few more points:
1) Now that the suspected batch numbers are not universal in causing the problem as all of us understand by now, and hoping that the places where they had the problem of serial endophs obtained genuine vials from authentic sources, can there be some other source of infection like the syringes used or the needles used? Request them to mention these also
2) There are many who are not still aware of such a serious situation and there are many who are still injecting daily and in bulk even after knowing the current situation!!! What can I say about them?!
3) I request some of the surgeons who are trying to help the other company people to take advantage of current scenario to abstain from such activity (like spreading rumours)
4) I got an information that the companys monopoly is getting over this year and another company (?Intas) is going to come up with the molecule Rb this year or next year. Hope we get some relief when that happens..
5) Till then, we should have the option of Avastin alive atleast for the sake of those patients who cant afford for multiple lucentis injections. So request all to fill the survey and help formulate most accepted way of practice.Camp for Children in BombayGetting felicitated. An honour for all of us.
These are the collated responses from 78 respondents. I am not interpreting the data and request all to exercise due care in interpreting data. I am presenting it as is. As elaborated by the VRSI in the letter, it appears that it could have been spurious drug and due diligence is advised in purchase and use of bevacizumab.
On analysing the data, it appears that most of us are sourcing it from reliable sources, given the paucity of cluster endophthalmitis. I have informed those who have had more than or equal to 3 cases in a year to look at their suppliers more carefully. There is a common link in supply as far as the recent cluster is concerned and I am sure that those involved are aware of the same and I have informed them of the same individually as well.