Dockets Management Branch (HFA-305)

Food and Drug Administration

5630 Fishers Lane, Room 1061

Rockville, MD 20852

**Docket No. 01D-0510, Draft Guidance for Industry, Integration of
Dose-Counting Mechanisms into MDI Drug Products, November 2001**

**Comments submitted electronically via e-mail 2/15/02, to
fdadockets@oc.fda.gov**

Dear Sir or Madam:

Boehringer Ingelheim believes strongly that patient safety is of
paramount importance. We understand that the guidance addresses an area
of concern for extended use drug products where patients currently may
not know when the product has reached the end of its use and further
dosing may provide sub-therapeutic amounts of medication. Therefore, we
welcome the publication of the draft *Guidance for Industry, Integration
of Dose-Counting Mechanisms into MDI Drug Products,* as it gives
manufacturers of metered dose inhaler and inhalation spray drug products
a better understanding of the requirements initially proposed in the two
chemistry, manufacturing and control guidances issued in 1998 and
1999[^1]^,^ [^2]:- i.e., "For MDIs, some kind of dose counter should be
considered".

Boehringer Ingelheim Pharmaceuticals, Inc. wishes to provide the
following general comments on the subject draft guidance.

**General Comments**

1.  The guidance specifically (and consistently) refers to dose counters
    as "integrated" into the MDI drug product. We are curious as to why
    the guidance does not allow for the use of an external dose counting
    device, and we wonder if the guidance intended to exclude the
    possible use of an external dose counter for MDIs. We are using the
    term "external dose counter" to mean commercial devices which attach
    to the canister or actuator of an MDI, but which are not an
    inseparable part of the MDI container/closure system.

> We suggest that adding a definition for an "integrated dose counter"
> to the guidance would be helpful.

2.  We believe the guidance should not be prescriptive in the design
    criteria for a dose counter (*e.g.*, "counts downward from the
    recommended number of actuations to zero"), but allow for
    alternatives and innovation in dose counting mechanisms.

3.  The guidance does not describe how a numeric dose counter might be
    used with MDIs all of which require priming/re-priming actuations
    where less than the full dose is delivered. In FDA's draft MDI
    Guidance, the information to be placed on the label includes the
    "number of **medication actuations** per container". We interpret
    that to mean that the priming/repriming actuations are not included
    in the labeled number of actuations. Since the dose counter will
    track all actuations, including those used for priming/repriming, it
    will not be consistent with the labeled number of medication
    actuations. It would be helpful if the guidance would address this
    discrepancy.

We wish to thank FDA for the opportunity to comment on this draft
guidance. Please contact the undersigned with any questions or comments
on this correspondence.

Sincerely,

George T. Chen, Ph.D.

DRA Senior Associate Director

Drug Regulatory Affairs

[^1]: "Draft" Guidance for Industry, Metered Dose Inhaler (MDI) and Dry
    Powder Inhaler (DPI) Drug Products, October 1998.

[^2]: "Draft" Guidance for Industry, Nasal Spray and Inhalation
    Solution, Suspension, and Spray Drug Products, May 1999.