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|                                 |               | # Paul Franz      |
|                                 |               |                   |
|                                 |               | # *Associate      |
|                                 |               |  General Counsel* |
|                                 |               |                   |
|                                 |               | 1 P&G Plaza       |
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|                                 |               | Cincinnati, Ohio  |
|                                 |               | 45202             |
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|                                 |               | tel 513 983-6084/ |
|                                 |               | fax 513 983-4274  |
|                                 |               |                   |
|                                 |               | franz.pa@pg.com / |
|                                 |               | www.pg.com        |
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November 19, 2004

Dockets Management Branch

Food & Drug Administration

Department of Human Services

Room 1061

5630 Fishers Lane

Rockville, MD 20852

Re: Docket Number 2003P-0366

Dear Sir or Madam:

Procter & Gamble submits this in response to Mylan Laboratories' October
29, 2004 filing in support of the Mattingly petition, citizen petition
No. 2003P-0075. The Mattingly petition asks the Agency to take the
literally unprecedented step of forcing a name change of a Rx-to-OTC
switch drug, so that the marketer could not use any form of the name of
the Rx product.

The new basis Mylan argues for this action is that a filing for a patent
extension stated that omeprazole and omeprazole magnesium are "different
active ingredients" for patent extension purposes. Mylan's letter adds
no new, relevant information justifying the extraordinary consumer
confusion that would result if P&G were forced to rename Prilosec OTC.

The Mattingly petition should be denied for the following reasons:

I.  TECHNICALITIES of patent-extension and drug-exclusivity law have no
    relevance to consumers, to therapeutic effect, or to product names.

> Whether an ingredient and its salt are legally the "same" or
> "different" depends purely on context. To illustrate: The Federal
> Circuit has recently held that drug active ingredients and their salts
> are the "same" for the purpose of defining the scope of extended
> patents. *Pfizer, Inc. v. Dr. Reddy's Laboratories, Ltd*., 359 F.3d
> 1361, 1366 (Fed. Cir.), *reh. den*. 2004 U.S. App. Lexis 10307 (2004).
> Under other precedent, omeprazole and omeprazole magnesium would be
> "different" active ingredients for purposes of determining eligibility
> for patent extension based on a regulatory review. *See* *Glaxo v.
> Quigg*, 706 F.Supp. 1224 (E.D. Va. 1989*) aff'd*, 894 F. 2d 392 (Fed.
> Cir. 1990).[^1] Active ingredients and salts are the same for purposes
> of determining the length of regulatory exclusivity for newly approved
> drugs. 21 USC Sec. 355(j)(5)(D).
>
> There is no question that omeprazole and omeprazole magnesium share
> the same "active moiety," that is, the same molecular form
> "responsible for the ... pharmacological action of the drug
> substance." See 21 CFR 314.108(a). Omeprazole magnesium is not a "new
> chemical entity" compared with omeprazole. *Id*.
>
> Mylan's letter, which relies selectively on one small element of this
> complex structure, adds nothing of substance to the Agency's careful
> consideration of the naming of Prilosec OTC.
>
> The consumer-relevant fact is that Prilosec Rx and Prilosec OTC share
> the same therapeutic moiety, which works the same way in each product.
> The Agency implicitly found this when it approved the labeling of the
> OTC product, which states that Prilosec OTC is "omeprazole
> delayed-release tablets 20 mg" with an active "equivalent to 20 mg
> omeprazole."

II. The Agency thoroughly considered the minor product differences
    between Prilosec and Prilosec OTC in allowing the name "prilosec
    OTC"

The Agency, as well as members of two Advisory Committees, relied on the
extensive safety database on Rx Prilosec capsules to approve Prilosec
OTC. Bioavailability studies were conducted to bridge the omeprazole Rx
capsule safety data to the omeprazole magnesium (Prilosec OTC) tablet
efficacy and safety data. As noted in our March 29, 2004 submission to
this Docket, the FDA's medical reviewer stated the following in the
public briefing materials for the October 20, 2000 Advisory Committee
meeting on the Prilosec Rx-to-OTC switch:

Results of bridging studies to compare Ome-Mg and Omeprazole indicate
their toxicokinetic and toxicological profile are equivalent.
Pharmacokinetic studies have demonstrated relative bioavailability
between Omeprazole capsules and Ome-Mg tablet formulations.

> It's therefore noteworthy (but not surprising) that the use of the
> Prilosec name for Prilosec OTC was not discussed as a concern by any
> committee members in two joint meetings of the Nonprescription Drugs
> Advisory Committee and the Gastrointestinal Drugs Advisory Committee,
> nor by any witnesses at those public hearings.
>
> The Agency's consideration of the minor differences between the two
> formulations was also illustrated through the requirement of
> demonstrating safe, effective and correct consumer usage of Prilosec
> OTC tablets, bearing a "Prilosec" name, in an OTC setting. In its
> response to the Andrx Citizen Petition, the Agency noted that this was
> achieved through five actual use studies and five label comprehension
> studies.[^2]

III\. It would be arbitrary for the Agency to deny the use of the name
"Prilosec OTC"

> It is arbitrary to treat similar situations differently. The use of
> the same tradename for acids or bases and their salts is common in
> both the Rx and OTC settings, and has been repeatedly approved by the
> Agency. The following are just a few examples:

+-----------------------+-----------------------+-----------------------+
| **Tradename**         | **Acid or base**      | **Salt**              |
+-----------------------+-----------------------+-----------------------+
| Proventil/Proventil   | Albuterol             | Albuterol sulfate     |
| HFA                   |                       |                       |
+-----------------------+-----------------------+-----------------------+
| Celestone             | Betamethasone         | Betamethasone sodium  |
|                       |                       | phosphate             |
+-----------------------+-----------------------+-----------------------+
| Cefobid               | Cefoperazone          | Cefoperazone sodium   |
|                       |                       | (salt sold under      |
|                       |                       | ingredient name       |
|                       |                       | "cefoperazone")       |
+-----------------------+-----------------------+-----------------------+
| Thorazine             | Chlorpromazine        | Chlorpromazine        |
|                       |                       | hydrochloride         |
+-----------------------+-----------------------+-----------------------+
| Tagamet               | Cimetidine            | Cimetidine            |
|                       |                       | hydrochloride         |
+-----------------------+-----------------------+-----------------------+
| Vibramycin            | Doxycylcine           | Doxycyline calcium    |
|                       |                       |                       |
|                       |                       | Doxycycline hyclate   |
+-----------------------+-----------------------+-----------------------+
| Edecrin               | Ethacrynic acid       | Ethacrynate sodium    |
+-----------------------+-----------------------+-----------------------+
| Cytovene/Cytovene IV  | Ganciclovir           | Ganciclovir sodium    |
+-----------------------+-----------------------+-----------------------+
| Haldol                | Haloperidol           | Haloperidol lactate   |
+-----------------------+-----------------------+-----------------------+
| Bactroban             | Mupirocin             | Mupirocin calcium     |
+-----------------------+-----------------------+-----------------------+
| Zofran/Zofran ODT     | Ondansetron           | Ondansetron HCL       |
+-----------------------+-----------------------+-----------------------+
| Advil/Advil Migraine  | Ibuprofen             | Ibuprofen (free acid  |
|                       |                       | and potassium salt)   |
+-----------------------+-----------------------+-----------------------+
| Children's Benadryl   | N/A                   | Diphenhydramine HCL   |
|                       |                       |                       |
|                       |                       | Diphenhydramine       |
|                       |                       | citrate               |
+-----------------------+-----------------------+-----------------------+

> The list could be readily expanded.
>
> Within the heartburn remedy category, the Agency has allowed the use
> of the Rx brand name in every Rx-to-OTC switch. This is true even
> though almost every previous switch did not switch an Rx strength
> product (unlike with Prilosec OTC), and even though the Rx and OTC
> indications are different.
>
> The relevant heartburn products and names are:

  ----------------------------------- -----------------------------------
  **Rx Tradename**                    **OTC Tradename**

  Pepcid                              Pepcid AC, Pepcid Complete, Maximum
                                      Strength Pepcid AC

  Tagamet                             Tagamet HB 200

  Zantac                              Zantac 75

  Axid                                Axid AR
  ----------------------------------- -----------------------------------

> Thus, if the Mattingly petition were granted, Prilosec OTC would be
> the only branded OTC acid reducer not sold under a variant of the Rx
> product's tradename.
>
> There is no evidence that the coexistence of all these products under
> the same root brand names (in some cases for nearly a decade) has
> caused any consumer harm or confusion.

IV\. It would be capricious for the Agency to revoke the use of the name
"Prilosec OTC"

> Omeprazole magnesium tablets were chosen for Prilosec OTC because the
> tablet form is consumer-preferred; the base ingredient in capsule form
> could have been more easily switched. There was no notice, throughout
> a regulatory review that included two advisory committee hearings,
> that use of the tablet form of magnesium salt would affect use of the
> word "Prilosec" in the product name. To deprive the sponsor of that
> use, after reliance on the Agency's decision, and subsequent very
> significant investment in the name, would be inequitable and
> capricious, particularly where, as here, the case for this
> unprecedented step rests on little more than irrelevant legalism.
>
> More significantly, massive consumer confusion would result from the
> forced renaming of what is now the best selling OTC heartburn remedy.
> The high consumer satisfaction with the product shows that the
> consumer harms asserted by Mylan simply don't exist. No basis exists
> for forcing consumers to search out a renamed brand, or for forcing a
> product marketer to establish a new brand name over a year after a
> significant product launch.
>
> Prilosec OTC is a version of Prilosec. Nothing in the Mattingly
> petition or Mylan's comments shows otherwise. The Mattingly petition
> should and must be denied.
>
> Respectfully submitted,
>
> Paul Franz
>
> Associate General Counsel

cc: Dr. Janet Woodcock

Jane Axelrad, Esq.

Dr. Charles Ganley

[^1]: The logic of *Glaxo* suggests that a different conclusion could be
    possible if approval of a salt preceded approval of an acid or base.

[^2]: CDER Memorandum, June 20, 2003, Dr. Charles Ganley's Response to
    Andrx's Citizen Petition.