Information Regarding Myozyme (alglucosidase alfa) - For Health Professionals

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Contact MHPD DPSC

May 3, 2007

To whom it may concern:

Subject: Recent reports of black particles after reconstitution of Myozyme

Genzyme has received isolated complaints pertaining to an observation of black gelatinous particles after reconstitution of 50 mg vials of Myozyme^® (alglucosidase alfa). Working in close consultation with relevant regulatory authorities, Genzyme immediately initiated an investigation and discovered that when certain types of needles are used to penetrate the rubber stopper on Myozyme vials, black gelatinous particles may appear in the product, on the stopper or on the needle. Although we have not received similar complaints with Genzyme's other products, we are writing to alert our customers to the potential that such particles might appear and to provide current advice and recommendations.

The black particles that were the subject of the Myozyme complaints were found to be composed of gel-like silicone with inclusions of microscopic stainless steel particles, both of which appear to have come from the needle. This gelatinous material has not been observed in product or on stoppers that have not been penetrated by a needle for reconstitution. Based on our investigations to date, the formation of the black particles is the result of the insertion of the needle through the stopper during vial reconstitution and is not related to the product.

Silicone is commonly used as a lubricant on needles and therefore silicone gel residue left on the bottom of the stopper after puncture by a needle is not a surprising phenomenon. However, the stainless steel particles that were observed in the context of this complaint have been attributed to burrs that flake off upon insertion and withdrawal of the needle from the stopper during reconstitution. To date, we have investigated a limited number of different needles in our laboratories in the USA and Europe. We have been able to reproduce this phenomenon, but it is not a consistent finding with all stainless steel needles or even with different lots of a particular needle that was observed to produce black particles. If black gel-like particles are noticed after reconstitution, sites should consider using a plastic needle or a plastic spike for reconstitution or an alternative brand of needle. However, if an alternative is not available, reconstituted solution should be visually examined for the presence of any foreign particles.

Our current advice and recommendations are as follows:

1. You must exercise particular care during reconstitution, dilution and administration including a visual examination of the reconstituted product, the product withdrawn into the syringe and during dilution into the infustion bag. Do not use a product with black particles after reconstitution.
2. Follow the reconstitution recommendations in the approved labeling and other guidelines (e.g. Insert, SmPC, Reconstitution and Administration Guide, etc), with specific reference to performing visual inspection of vials following reconstitution.
3. This phenomenon has the potential to occur with any stainless steel needle. If you observe this phenomenon during or after reconstitution, we recommend that you discard the vial and use a plastic needle, a plastic spike or a different brand of needle to reconstitute a new product vial. In addition, we recommend that the same needle be used once, as multiple uses of the same needle can lead to stopper coring and other problems. Please review needle product labeling, compendia and other appropriate sources for limitations and instructions on re-use of needles.
4. An inline low protein binding 0.2μm filter should be used to filter the reconstituted product during administration.
5. Unused vials or reconstituted product should be refrigerated within the conditions specified in the approved labeling.

We have also informed regulatory authorities of the results of our investigation, and of our intention to provide this information to our customers. We will keep you informed should our investigation reveal any additional pertinent information. The reports of black gelatinous particles are currently limited to one Genzyme product. However, as a precaution for other products, please follow the recommended procedures as outlined above to ensure that there is minimal risk to patients.

Should you require further information or have any questions please don't hesitate to contact us at contact us at (800) 745-4447 and select option 2 if calling in the US and Canada, or +31356991499 if calling in Europe. We can also be reached by email at medinfo@genzyme.com or eumedinfo@genzyme.com.

Yours sincerely,

original signed by

Cheryl Marotta
Vice President, Quality Operations
Genzyme Corporation