April 24, 2014

Robin Chiponski
Director General
Health Canada
250 Lanark Avenue
Ottawa, Ontario K1A 0K9

Dear Ms. Chiponski:

Re: Request for immediate reinstatement of Biolyses EL

Overview
Biolyse Pharma Corp. (Biolyse) is an established biotech manufacturer based in St. Catharines.
Biolyse manufactures and distributes the anti-cancer drug Paclitaxel for injection. Paclitaxel is a
chemotherapy drug used to treat a wide variety of cancers, including ovarian, breast, and lung
cancers. Every year, the Paclitaxel produced by Biolyse helps save or extend the lives of between
7,000 and 10,000 Canadian cancer patients.
Since entering the market in 2001, Biolyse has reduced the price of Paclitaxel from $3,000 per
treatment session to $50 per treatment session. This has made this life-saving drug much more
readily available to Canadian cancer patients. The use of this drug has increased three fold since
Biolyse has been on the market. As a result, Biolyse now manufactures and distributes over 80%
of the Paclitaxel used in Canada.
On April 11, 2014, Health Canada suspended Biolyses Establishment Licence (EL) without
hearing, under subsection C.01A.017(1) of the Food and Drug Regulations (FDR), following
an inspection during which inspectors attributed Risk 1 classification to six observations.
We are requesting that Health Canada reconsider the immediate suspension of Biolyses EL and
reinstate the licence immediately, for the following reasons:
Paclitaxel produced by Biolyse is safe. It does not present any risk of injury to the health
of Canadians.
The six observations that were classified as Risk 1 should not have been classified as
Risk 1, pursuant to Health Canadas policies.

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The six Risk 1 observations have in any event been addressed and corrected by Biolyse.
Health Canada has not complied with its own procedures in conducting the inspection of
Biolyse.
Biolyse will likely be forced to cease operations permanently, throwing 60 highly trained
people out of work in St. Catharines.
Some hospitals have run out of Paclitaxel and are turning patients away. Overall, supplies
of Paclitaxel in hospitals are already running low. If Biolyse is not able to manufacture
and distribute Paclitaxel, shortages of this drug will interrupt the treatment of cancer
patients across the country and will hinder their recovery, and negatively impact
outcomes.
Each of these reasons is addressed more fully below.
Biolyse is also requesting a meeting with Health Canada at your Ontario Region offices by April
28, 2014, to present its corrective actions to the six Risk 1 Observations.
Biolyses Paclitaxel is safe
Paclitaxel produced by Paclitaxel is safe:
There has never been a failure to the sterility of the finished product in any batch of
Paclitaxel produced by Biolyse.
Paclitaxel for injection is a category 1 product according to USP 51 because of its
inherently anti-microbial activity. The excipient contains approximately 50% ethanol and
50% Cremophor. Neither supports microbial growth. The product is administered through
an in-line filter with a microporous membrane not greater than 0.22 microns.Nonetheless,
Biolyse manufactures the product with the same great care as it would a water based
product using a highly controlled manufacturing process. The product, once sterilized, is
filled, stoppered and crimped under aseptic conditions. All critical operations are
performed in a setting that meets the GMP requirements of a Grade A environment.
There is no evidence whatsoever indicating any contamination of the product. There have been
no reports from hospitals, doctors, or patients of any problems with Paclitaxel produced by
Biolyse. There is, in short, no evidence of any risk of injury to the health of patients using this
drug that would make it necessary to suspend Biolyses licence immediately.
The Observations should not have been classified as Risk 1
Biolyse is contesting the classification of six Observations as Risk 1.
The six 6 Risk 1 Observations are conditions that remain unchanged since they were first
approved by Health Canada when it granted Biolyse its Establishment Licence in J anuary 2010.
Those same conditions were reviewed again by Health Canada, without comment, in inspections
in 2012 and 2013. As neither Biolyses operations, nor the applicable guidelines have changed, it
appears that Health Canada has changed its assessment standards without alerting Biolyse.
The six Risk 1 Observations ought not to have been assigned a Risk 1 rating. A Risk 2 rating was
the highest rating that could be justified under Health Canadas own guidelines. There is no
justification or explanation provided for raising these observations to Risk 1. These points are

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discussed in further detail in our letter to Health Canadas Ontario Regional Director,
Compliance and Enforcement, Ken Moore, attached.
The Risk 1 Observations have been corrected
Biolyse has retained consultants who have worked with Biolyses own experts. They have
addressed each of the six Risk 1 Observations in the Inspection Exit Report. Corrective action
has been implemented.
Health Canada did not comply with its own procedures
Health Canada did not comply with its own procedures in conducting the inspection of Biolyse:
Health Canadas policy, Risk Classification of Good Manufacturing Practices (GMP)
Observations (GUI-0023) (Risk Classification Policy), provides that Risk 1
observations will be brought to the attention of the company being investigated
immediately.
This policy was not complied with. At no time during the inspection did the inspectors
advise Biolyse that they perceived any risk 1s. Biolyse asked the inspectors as they
concluded the inspection whether there were would be any risk 1 observations. The
response was that the inspectors had not seen any risk 1 situations. The classification of
six Observations as Risk 1 was first brought to Biolyses attention in the draft Inspection
Exit Report sent on March 12, 2014.
Section 6.2.1 of the Drug Good Manufacturing Practices (GMP) and Establishment
Licencing (EL) Enforcement Directive (POL-0004) (Enforcement Directive) requires
that if Health Canada intends to maintain an NC rating, the Inspector and/or Operational
Manager will communicate with the establishment to inform them of the intent to
maintain the NC rating and will provide the establishment with an opportunity to meet
with them.
Health Canada did not comply with this requirement before finalizing the Inspection Exit
Report.
Economic impact of suspension of Biolyses licence
Biolyse will likely be forced to cease operations permanently if its licence is not reinstated
without delay. Health Canadas Risk Classification Policy recognizes that the suspension of an
EL is a serious consequence for a company. In Biolyses case, it shuts off Biolyses revenue and
potentially gives rise to liabilities to customers whose orders Biolyse is unable to fill. The
inevitable result is that Biolyse will at some point be forced to cease operations permanently.
Biolyse has already laid off most of its staff. Its failure would result in 60 highly trained people
losing their jobs in St. Catharines, as well as indirect economic losses resulting from the failure
of an important employer in St. Catharines.
Risk of injury to the health of Canadians if Biolyses EL is not reinstated
Biolyse recognizes that the most important consideration is the health of Canadians who depend
on the life-saving cancer drug Paclitaxel.

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Biolyse has been fielding calls from hospitals over the last week. Paclitaxel is manufacturerd and
distributed on a just-in-time basis. Stocks at some hospitals have already run out and patients are
being turned away. Distributors are running low or have run out.
One of Biolyses distributors, RXSource, has approximately one and a half weeks supply of
Paclitaxel. However this is not available to hospitals because Health Canada has ordered
RXSource not to distribute it. Biolyse has approximately one months supply of Paclitaxel.
However, the suspension of Biolyses EL means that this product cannot be distributed to
hospitals.
It is not clear that sufficient alternative supplies are available to avoid the shortages that will
soon develop. Even if there are alternative supplies, they are not economic: Hospiras list price is
about $4,000 per treatment cycle, as compared with the $50 per treatment cycle charged by
Biolyse. Other suppliers will maintain this higher price as long as possible, dramatically
affecting hospital budgets.
There is no guarantee that this American company is able to supply the totality of the Canadian
market on such short notice, since it is known that in the past they had numerous drug supply
problems.
Because there is a lead time of three and a half weeks to produce and distribute fresh Paclitaxel,
unless Biolyses EL is reinstated immediately, shortages are inevitable, even if all existing
product at RXSource and Biolyse is released.
As a result, Canada faces an imminent coast-to-coast shortage of an important, life-saving cancer
drug.
This shortage will interrupt treatment schedules of cancer patients. Since treatment schedules are
critical to the success of cancer treatments, this shortage will likely negatively impair treatment
outcomes.
To put it bluntly, Health Canadas suspension of Biolyses EL will injure the health of Canadian
cancer patients, and may cause deaths.
Biolyse submits that the injury to the health of Canadians that the suspension of its EL will cause
must be weighed against the likelihood and severity of any injury to the health of Canadians that
could result from the observations classified as Risk 1.
Biolyse submits that any risks of injury from reinstating its EL is extremely low. The Risk 1
Observations relate to (alleged) deficiencies in studies designed to prove Biolyses compliance
with GMP. None of the observations points to any actually unsafe conditions in Biolyses
facility. None of the observations suggests any contamination of the product. As indicated above,
Biolyse has never experienced a failure relating to the quality of its product. ,
We note that Health Canada has not ordered a recall of Paclitaxel. This suggests that Health
Canada shares Biolyses evaluation that it would cause more harm to remove Paclitaxel from the
market. The same evaluation should apply to the manufacture of Paclitaxel by Biolyse.
The FDR make it clear that the immediate suspension of an EL is an extraordinary measure. The
normal process under the Regulations where an NC rating is applied is to follow the process in
C.01A.016(3), which requires that Health Canada provide the licensee with reasons, an
opportunity to implement corrective actions, and a hearing. Immediate suspension under

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C.01A.017 is an emergency process that is only available if it is necessary to prevent injury to
the health of the consumer.
Biolyse submits that the immediate suspension was not necessary to prevent injury to the health
of the consumer.
It is critical to address this issue immediately. If Biolyses EL is reinstated immediately, serious
shortages can be still avoided. If it is not, Canada faces an immediate, national, cancer health
care crisis.
Relief requested
At this time, Biolyse is requesting that Health Canada reinstate its EL immediately. If Health
Canada is not prepared to reinstate Biolyses EL immediately, it should immediately permit the
distribution of Paclitaxel in stock at Biolyse and RXSource.
Biolyse also requests the opportunity to meet with Health Canada at the Ontario Region office on
Monday, April 28, 2014, to present its corrective actions. Biolyse requests that the inspectors as
well as the Regional Director, Compliance and Enforcement (Ken Moore) attend this meeting.
Biolyse is confident that it can satisfy Health Canada on each of the six Risk 1 Observations, and
expects that following this meeting, its licence will be reinstated immediately following the
meeting (if it is not reinstated before).

Yours very truly,

Brigitte Kiecken
President

cc. Ken Moore, Regional Director, Compliance and Enforcement, Health Canada









April 22, 2014


Ken Moore
Regional Director, Compliance and Enforcement
Health Canada, Ontario Region
180 Queen Street West
Toronto, Ontario M5V 3L7

Dear Mr. Moore:

Re: Inspection Exit Report dated April 11, 2014
Overview

Biolyse Parma Corporation (Biolyse) contests the assignment of the Risk 1 rating to
Observations 1-6.

Biolyses position is as follows:

Observations 1-6 are conditions that remain unchanged since they were first approved
by Health Canada when it granted Biolyse its Establishment Licence in January 2010.
Those same conditions were reviewed again by Health Canada, without comment, in
inspections in 2012 and 2013. As neither Biolyses operations, nor the applicable
guidelines have changed, it appears that Health Canada has changed its assessment
standards without alerting Biolyse.

Observations 1-6 ought not to have been assigned a Risk 1 rating. A Risk 2 rating was the
highest rating that could be justified under Health Canadas own guidelines. There is no
justification or explanation provided for raising these observations to Risk 1.

Because of the 10 day deadline established by Health Canada, as well as the need to address
the levels applied to the observations in the Inspection Exit Report through a Corrective and
Preventative Plan of Action, this submission is limited to the observations that were classified
as Risk 1. Biolyse also intends to contest certain Risk 2 ratings assigned to observations in the
Inspection Exit Report. Biolyses position in relation to these observations will be forthcoming
at a later date.
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Attribution of Risks to the Observations

Health Canadas policy, Risk Classification of Good Manufacturing Practices (GMP) Observations
(GUI-0023) (Risk Classification Policy) sets out the principles to be followed in attributing risk
levels to observations.

The Risk Classification Policy recognises that:

Attribution of a NC rating may have serious consequences for a
company, ranging from the implementation of important
corrective measures to the temporary suspension or termination
of the Establishment Licence (EL). Therefore, these situations of
non-conformity have to be well defined, unambiguous and
directly supported by the applicable regulations.

As outlined in more detail below, the alleged situations of non-conformity outlined in the
observations of the Inspection Exit Report are poorly defined, ambiguous, and not always
directly supported by the applicable regulations.

In particular, Health Canada generally did not support the Observations or Risk ratings in the
Inspection Exit Report by reference to applicable regulations or to either the Good
Manufacturing Practices (GMP) Guidelines 2009 Edition, Version 2 (GMP Guidelines) or the
Risk Classification Policy.

Previous inspections of Biolyse and lack of uniformity among inspectors

The purpose Risk Classification Policy includes: To ensure uniformity among the inspectors of
the Health Products and Food Branch Inspectorate (Inspectorate) in the attribution of the rating
following establishment inspections.

Health Canada first issued an Establishment Licence (EL) to Biolyse on January 21, 2010, after
a thorough inspection of Biolyses facility. Biolyse was inspected in 2012 and 2013. Biolyse was
rated Compliant after both of those inspections. None of these inspections resulted in Risk 1
observations. All observations were Risk 2 or lower. All observations were addressed promptly
by Biolyse. Also, around March 2013, Health Canada Inspectors were present at Biolyse to
witness sterile fill activities of a batch being manufactured. They had no negative comments.

Biolyse has not made any changes to its facility nor to its sterile manufacturing personnel. The
aseptic process has remained the same, apart from some minor improvements suggested by
past inspectors.

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Neither the GMP Guidelines, nor the Risk Classification Policy have been amended since Health
Canadas first inspection of Biolyse.

All of the Risk 1 observations in the Inspection Exit Report represent conditions that have
existed since Biolyse first received its licence. In other words, Health Canadas inspectors
observed those conditions in the 2010, 2012, and 2013 inspections, and did not draw any
formal Observations from them. The fact that Health Canada is not attributing Risk 1
classification and an NC rating to conditions that it previously considered compliant represents
a major change in Health Canadas approach to the GMP Guidelines and the Risk Classification
Policy as they apply to Biolyse. If Health Canada intended to change the rules applicable to
Biolyse or the industry generally, it should have given the Biolyse or the industry generally prior
notice of these changes by amending the GMP Guidelines or the Risk Classification Policy.

Observation # 1
Risk 1
Sterile products - C.02.029

Inspectors comment from the Inspection Exit Notice:
There was no documented evidence that airflows within room 201-IFill (Grade A Class 100
area) were sufficient to protect product from potential contamination (i.e. unidirectional flow
with the appropriate sweeping action away from filling/closing areas.

Biolyse response:

1. Airflow studies are not referenced in the Risk Classification Policy. However,
observations relating to environmental monitoring are listed as Risk 2 observations. For
example, Insufficient number of samples taken for environmental
monitoring/inadequate sampling methods. (), is a Risk 2 Observation.
2. This Observation is based on the inspectors dissatisfaction with one video of a fog test.
The fog test was performed using CO
2
fog, which dissipates quickly due to air velocity in
the tested areas. As a result, it is difficult to capture on film. On April 9, Health Canada
asked Biolyse to repeat the fog test. Health Canada did not give Biolyse time to do this
however, as it proceeded to finalize the Inspection Exit Report and suspend Biolyses
licence on April 11. In any event, concerns about one fog test are not a sufficient basis to
classify an observation as Risk 1.
3. The inspectors did not give sufficient weight to other evidence regarding airflow
provided by Biolyse. This is inconsistent with the GMP Guidelines, which require that
maintenance of unidirectional air flow should be demonstrated and validated, but
does not prescribe particular tests as being the only acceptable way to demonstrate
4

airflow. Moreover, Health Canadas guide, Process Validation : Aseptic Processes for
Pharmaceuticals (GUI-0006) refers to a number of methods for validating airflow.
4. In the initial commissioning of the clean room in 2009-2010 Biolyse performed all
necessary work to confirm the quality of air flow, including fog tests. Health Canada
reviewed and accepted these results, and licensed the facility. Unfortunately the original
fog test could not be located by either Biolyse or Health Canada during the 2014
inspection. Nevertheless, Biolyse presented demonstration of the environmental
conditions for aseptic operations at the time of inspection, including two new fog tests.
5. The data presented included the most recent results from Biolyses re-test program.
This program was established by Biolyse after it received its EL. This re-test program
includes scheduled air filter tests by a certified agency, air velocity testing, room air
change verifications, particle count monitoring and continuous room pressure
differential monitoring. Re-qualifications and constant monitoring of all areas of the
clean room are performed using appropriate testing methods. Data reported
demonstrates conformance to the requirements as set out in section C.02.029 of the
GMP Guidelines. Unidirectional airflow in the I fill room (the sterile room) is beyond the
required >0.45 meters/second 20% at the working position. Data also demonstrates
that the air has remained within the initially established parameters and that all areas of
the clean room are suitable in terms of local and background environments.
6. As well, visual static and dynamic air flow studies (fog test) were made available during
the inspection. However visualization (fog test) is not specified as a yearly
requirement in the GMP guidelines.
7. Overall, the data presented was sufficient to support adequate environmental
conditions for aseptic operations, that there was no immediate or latent health risk and
that the drug would meet its marketing authorization. This observation should be
classified as Risk 2, at the highest.

Observation # 2
Risk / 1
Sterile products / C.02.029

Inspectors comment: The design of the facility did not provide adequate control of viable
microorganisms and non-viable particulates during critical operations resulting in a potential
risk of product contamination.

Biolyse response:

1. Inadequate control of viable microorganisms is a Risk 2 Observation pursuant to the Risk
Classification Policy:
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Insufficient environmental controls/Insufficient monitoring for
viable microorganisms during filling for aseptically filled products.
()Premises and equipment not designed or maintained to
minimize contamination/generation of particles. ()

The Risk Classification Policy requires that if a Risk 2 classification is upgraded to Risk 1,
a proper explanation will be provided to the establishment. Health Canada did not
comply with this requirement, and has not explained why this Risk 2 Observation should
be upgraded to Risk 1.

Similarly, the examples provided in relation to this observation are either not classified
in the Risk Classification Policy, or they are classified as Risk 2 Observations. They are
not classified as Risk 1 Observations. In particular, the example relating to crimping is
classified as Risk 2 (Inappropriate environment/controls for crimping following aseptic
filling.), and is not upgradeable to Risk 1.

2. Microbial limits set out for the entire aseptic area, background included, are the same
as the limits required by the GMP guidelines for a Grade A area. There are no microbial
limits that fall under a Grade B classification in the entire aseptic processing area. Work
stations within this sterile environment are defined by areas located directly under
HEPA filters that are used for critical activities such as filtration, fill, capping, crimping
and material holding. These areas have a higher unidirectional air flow velocity to
ensure the absence of non-viable particulates. Controls of both viable and non-viable
particulates are in place and support adequate environmental conditions for aseptic
operations. There is no evidence that the drug produced represents an immediate or
latent health risk or that it would not meet its marketing authorization.

Observation # 3
Risk / 1
Sterile products - C.02.029

Inspectors comment: Biolyses aseptic processes simulation (media fill) program failed to
adequately assess its aseptic processing capabilities.

Biolyse response:
1. This observation is not classified as Risk 1 by the Risk Classification Policy. Deficiencies
relating to aseptic process simulation (media fill) are classified as Risk 2 by the Risk
Classification Policy: Inadequate program for media fill is classified as Risk 2. By
contrast, the complete lack of media fills would constitute a Risk 1 Observation,
according to the Risk Classification Policy. There is therefore no basis to categorize the
deficiencies alleged as Risk 1.

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The examples provided by the inspectors are also classified as Risk 2, to the extent that
they are classified at all. For example:

Example 1: failure to mimic all aseptic steps. This example appears to relate to non-
validated time lapses after sterilization, which are classified as Risk 2 (non-
upgradeable):

Non-validated time lapse between cleaning, sterilization, and use
of components, containers and equipment.

Non-validated time lapse between start of manufacturing and
sterilization or filtration.

Example 2: Media sterilization deficiencies alleged by Health Canada are not
classified as Risk 1. Similar observations are classified as Risk 2 by the Risk
Classification Policy.
Example 3: Inadequate Study Frequency: inadequacies relating to sampling and
monitoring are classified as Risk 2 in the Risk Classification Policy. This observation
was brought up in a 2012 inspection. The company explained that due to the small
amount of production batches being produced that it wanted to perform only one
media fill. The suggestion was found acceptable in the closing of the 2012 Exit
Notice. In the 2013 inspection there was no observation relating to the accepted
one media per year. We assume that Health Canada does not intend to resile from
its earlier acceptance of annual testing without prior notice to Biolyse. Accordingly,
this observation should be removed.
Example 4: was resolved during the inspection.
Example 5: Interventions Control Deficiencies: deficiencies relating to media fill
programs are classified as Risk 2.
Example 6: At the worst this should fall under risk 2 in the inadequate program for
Media fill.
Example 7: At the worst this should fall under risk 2 in the inadequate program for
Media fill. (Resolved during inspection)
Example 8: At the worst this should fall under risk 2 in the inadequate program for
Media fill. (Resolved during inspection)
It has been mentioned that #7 and 8 have been addressed by the modification of the
protocol.

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2. Biolyse was operating in accordance with their media fill protocol that was reviewed by
Health Canada in previous inspections. Media fill data to support proof of adequate
environmental conditions for aseptic operations was sufficient to support that there was
no immediate or latent health risk and that the drug would meet its marketing
authorization.

Observation # 4
Risk 1
Sterile products - C.02.029

Inspectors comment: The environmental monitoring program failed to demonstrate that the
facility was maintained and controlled to prevent microbiological contamination of sterile
parenteral products

Biolyse response:

1. Deficiencies in the environmental monitoring program are classified as Risk 2 by the Risk
Classification Policy:

Insufficient number of samples taken for environmental
monitoring/inadequate sampling methods. ()

Insufficient environmental controls/Insufficient monitoring for viable
microorganisms during filling for aseptically filled products. ()

Although such deficiencies can be upgraded to Risk 1, Health Canada has not provided
the rationale for the upgrade, as required by the Risk Classification Policy.

An upgrade is not justified here, given that Biolyse resolved some of Health Canadas
concerns either completely, or partially, during the inspection.

2. Biolyse provided Health Canada with adequate environmental monitoring (EM) that fall
within the requirements of the GMP guidelines. The EM program is supported by trend
reports that demonstrate and support that the aseptic operations are more than
adequate and that there are no immediate or latent health risk and that the drug would
meet its marketing authorization.

Observation # 5
Risk / 1
Sterile products / -C.02.029

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Inspectors comment: The observations illustrate a lack of control and reliability with respect to
the generation and reporting of the microbiological data used to support aseptic manufacturing
control and product release.

Biolyse response:

1. Deficiencies in generation and reporting of microbiological data are classified as Risk 2,
to the extent that they are classified. For example:

Capability of media to grow a wide spectrum of microorganisms
not demonstrated.

Samples for sterility testing insufficient in number or not
representative of the entire production run.

2. Product release and environmental testing methodologies have always remained the
same and reflect marketing authorization. Microbiology activities noted in the
observations are based on widely accepted procedures. A PhD in microbiology with
over thirty five years of experience in the field is in charge of the microbiology
laboratory. Sufficient scientific evidence was provided to support all technical decisions.
There is adequate data to support that there was no immediate or latent health risk and
that the drug would meet its marketing authorization.

Observation # 6
Risk 1
Quality control department C.02.015

Inspectors comment: The laboratory systems and controls in place for the proper qualification,
operation, calibration and maintenance of equipment, documentation of testing results and
securing of raw data did not assure that the results and conclusions generated were accurate,
precise and reliable.

Biolyse response:

1. The alleged deficiencies with Biolyses laboratory systems and controls are not classified
as Risk 1 Observations by the Risk Classification Policy. Analogous deficiencies are
classified as Risk 2 by the Risk Classification Policy. For example, the following are
classified as Risk 2:

Inadequate facilities, personnel and testing equipment.

For testing laboratories (in house or contract), the systems and
controls in place for the proper qualification, operation,
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calibration and maintenance of equipment, standards, solutions,
and records keeping do not assure that the results and
conclusions generated are accurate, precise and reliable. ()

2. All observations were addressed prior to the closing of the inspection. The analyst in
charge of Quality Control has provided evidence that testing can be traced and those
results are stored in a traceable manner. There were sufficient controls in place to
support proof that the production and testing of the drug consistently meets its
marketing authorization and does not represent an immediate or latent health risk.

Health Canada did not give Biolyse sufficient time to address requests for additional
information
On April 9, Health Canada provided Biolyse with a response to its corrective action letter. This
response, in the form of a table, contained numerous comments under the heading Deficiency
/ Request for Additional Information.

Biolyse assumed that Health Canada intended to allow Biolyse sufficient time to address and
respond to these comments before closing the inspection and finalizing the Inspection Exit
Report. Biolyse was therefore surprised when Health Canada finalized the Inspection Exit
Report with an NC rating two days later. Health Canada finalized the Inspection Exit Report with
an NC rating without providing Biolyse with an opportunity to meet with the Inspector and/or
Operational Manager as provided for in the Drug Good Manufacturing Practices (GMP) and
Establishment Licencing (EL) Enforcement Directive (POL-0004).

Biolyse remains committed to addressing each observation made by the inspectors in a manner
that completely satisfies Health Canada in order to continuously improve Biolyses facility.
Nevertheless, Biolyse expects Health Canada to deal with it fairly and to follow its own policies
in conducting inspections and classifying risks.

Biolyse therefore requests that Observations 1-6 be reclassified as Risk 2 or lower.

Yours very truly,

Brigitte Kiecken
President
Biolyse Pharma